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Case 1: 48-Year-Old Patient With HER2+ Metastatic Breast Cancer

EP: 1 . Best Practices: HER2+ MBC With Brain Mets

EP: 2 . Frontline Standards of Care for HER2+ MBC

EP: 3 . Case 1: 48-Year-Old Patient With HER2+ Metastatic Breast Cancer

EP: 4 . Treatment Strategies for Relapsed/Refractory HER2+ MBC

EP: 5 . Case 2: 61-Year-Old Patient With R/R HER2+ MBC

EP: 6 . Cancer Network Around the Practice: Relapsed/Refractory HER2+ Metastatic Breast Cancer

Adam M. Brufsky, MD, PhD: Let’s talk about this case. This is a 48-year-old woman who presented to her primary care physician a number of years ago with a lump in her breast. She had a 4.4-cm left breast mass and 3 palpable axillary lymph nodes. Her ultrasound and mammogram confirmed these physical findings.

She was referred to a medical oncologist and had a core needle biopsy that showed ER- [estrogen receptor-negative]/PR- [progesterone receptor-negative], HER2 [human epidermal growth factor receptor 2]-positive by IHC [immunohistochemistry score] that was 3+. A CT scan of the chest, abdomen, and pelvis showed 3 liver lesions, the largest being 3.1 cm. This is the de novo patient we always talk about. She had an MRI of the brain and it was negative for metastasis. She received 6 cycles of THP [docetaxel, trastuzumab, pertuzumab], followed by HP [trastuzumab, pertuzumab] for another 12 months. That’s 18 months of therapy.

She had a partial response in her breast mass, and her liver lesions fully responded. Later, she suddenly began to have rapid unexplained weight loss. The CT scan only showed 2 new liver lesions, so not quite the symptom I would imagine. She then got a brain MRI that showed about 30 widely scattered lesions, the largest being about 0.5 or 0.6 [cm]. They have all these little punctate ones; you’ve all seen those.

The question is: what treatment would you give this person? Let’s say the brain MRI shows 3 lesions, all in the frontal cortex, with the largest being 1.5 cm. That makes it a little bit of a different question because if there are widely scattered lesions, we’re not going to want to do SRS [stereotactic radiosurgery]. We are probably going to want to do whole brain radiation. Let’s say she’s asymptomatic with no edema. The polling question is: what treatment would you recommend? T-DM1 [trastuzumab emtansine], tucatinib/trastuzumab/capecitabine, SRS to the brain metastases, clinical trial, or other.

You guys could answer that question. Let me start with Sara. How would you approach this?

Sara A. Hurvitz, MD, FACP: They’re not totally mutually exclusive, right? You could do SRS and switch systemic therapy. She is progressing systemically in the liver, so I think switching systemic therapy makes sense. I like tucatinib because it does penetrate the blood-brain barrier, but I would still be tempted and would probably talk to my radiation oncology and neurosurgery colleagues. We’d probably end up doing both the SRS and tucatinib-based therapy.

Adam M. Brufsky, MD, PhD: That’s reasonable. VK, do you have any other comments on this?

VK Gadi, MD, PhD: Yes, I agree. The tolerability of the regimen is good. You might even give this lady an opportunity to fly without SRS and have that in your back pocket. If you’re not seeing control, you can go to SRS at a later time. I don’t think there’s a wrong answer here. You could probably do it both ways.

Adam M. Brufsky, MD, PhD: Neil, do you have something to add?

Neil M. Iyengar, MD: No. She fits perfectly into the HER2CLIMB population, so I agree with everything that has been said because there is demonstrated activity of the tucatinib-based regimen in terms of CNS [central nervous system] response. Coupling that with SRS is reasonable. This is the patient we were talking about earlier with whom we would discuss foregoing local therapy to the brain. That’s a reasonable discussion here. It’s a tricky poll question because my kneejerk response would be to put her on a clinical trial. We should all be trying to prioritize clinical trials, but in the absence of that clinical availability, tucatinib plus or minus radiation is a reasonable option.

Adam M. Brufsky, MD, PhD: There’s a clinical trial that’s great; it’s not scientifically spectacular, but clinically, it’s fabulous. I believe it’s called DESTINY. In fact, I put a patient on it today with trastuzumab deruxtecan and tucatinib together. That’s a great trial that’s going to accrue quickly. If we could put as many people as we can on that, we can answer the clinical question quickly. I would agree.

I have 1 last question before we go on to the last 25 minutes and the last segment. What do you tell people about [adverse] effects? Are you seeing a lot of [adverse] effects with tucatinib? Do you have to dose reduce it at all when you give it? These are questions people who haven’t had a lot of experience with it usually ask. I’ll start with Neil. Do you see a lot of diarrhea? Do you have to dose reduce with tucatinib?

Neil M. Iyengar, MD: In my experience, this regimen is quite tolerable. We all, as oncologists, have unfortunately become very comfortable with managing diarrhea, along with oncology nursing and so forth. What I have found with the tucatinib-based regimen is that with the initiation of antidiarrheal agents, the diarrhea usually resolves or improves pretty quickly. People have to know about it and be prepared to deal with it immediately. It does come on early, usually within the first cycle.

The other consideration to keep in mind with tucatinib is that many of the [adverse] effects are likely related to capecitabine. We’re all very comfortable with managing capecitabine-related toxicity and dose modifying capecitabine as needed. We see in the HER2CLIMB data that patients in the tucatinib arm stayed on study longer and were therefore exposed to capecitabine for longer than those in the placebo arm. I think a lot of the toxicities are familiar ones that are related to capecitabine and are quite manageable.

Adam M. Brufsky, MD, PhD: Great. VK and Sara, do you have any other comments about this toxicity? Do you see any toxicity at all with this, more than you’d expect?

Sara A. Hurvitz, MD, FACP: It’s well tolerated. About 13% had grade 3/4 diarrhea. Before getting on this call, I had to dose reduce a patient on this therapy. It’s hard to tell. On the clinical trial we enrolled patients, and I had a patient on who had severe colitis, hospitalization, etc, and I was sure she was getting tucatinib. When she was unblinded after the data came out, it turned out that she wasn’t on tucatinib. She was on placebo. I completely agree that these are [adverse] effects we’re used to with capecitabine. There’s not a whole lot of difference. Tucatinib is pretty well tolerated.

VK Gadi, MD, PhD: I agree. I think the capecitabine is the real culprit. The people on the trial were actually on it for so much longer that the toxicities from capecitabine emerged ongoing on the study. That has been my experience. Something important we don’t yet have is the PRO [patient-reported outcomes] data from these studies. A lot of my colleagues, especially those in communities where patients come in from a long way away, know that this is a tremendous pill burden with this regimen. Sometimes a parenteral regimen that you’re giving every 3 weeks is better for patients. I’m curious to see what those data look like when they come out. From our perspective as physicians, this is a slam dunk and it’s easy to give, but that’s not always the perspective that matters.

Adam M. Brufsky, MD, PhD: I agree.

Sara A. Hurvitz, MD, FACP: Yes, I think the quality of life PRO data were presented at the San Antonio [Breast Cancer Symposium]. I’m trying to pull it up. I don’t have it right at my fingertips, but my recollection was that it looked fairly good, that the quality of life was maintained.

Adam M. Brufsky, MD, PhD: Right, but they’re not going to tell you that they’re struggling to take all those pills. It’s a lot.

Sara A. Hurvitz, MD, FACP: That’s true.

Adam M. Brufsky, MD, PhD: It’s about 9 pills a day, which is a lot.

Neil M. Iyengar, MD: The quality of life data are always interesting because the end point of choice is time to deterioration and whether we are avoiding that. I think that’s a fairly low bar.

Adam M. Brufsky, MD, PhD: Exactly. Women are going to do anything they can.

Transcript edited for clarity.

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Patient Case Presentation

Patient Mrs. B.C. is a 56 year old female who is presenting to her WHNP for her annual exam. She had to cancel her appointment two months ago and didn’t reschedule until now. Her last pap smear and mammogram were normal. Today, while performing her breast exam, her nurse practitioner notices dimpling in the left breast as the patient raises her arms over her head. When the NP mentions it to Mrs. B.C. she is surprised and denies noticing it before today. A firm, non-tender, immobile nodule is palpated in the upper quadrant of her breast . The NP then asks Mrs. B.C. how frequently she is performing breast self-exams, she admits to only doing them randomly when she remembers, which is about every few months. She reports no recent or abnormal drainage from her breast. Further examination reveals palpable axillary lymph nodes. 

Mrs. B.C. is about 30 pounds overweight and walks her dog around her neighborhood every morning before work and every evening when she gets home. She reports drinking a glass of white wine before bed each night. She denies any history of tobacco use. She reports use of a combination birth control pill on and off for 25 years until she reached menopause. She is not currently taking any prescription medications. 

Past Medical History

• Menarche (Age 10)
• Post-menopausal (Age 53)
• No other pertinent medical history

Family History:

• Father George- deceased from stroke (75 years old), history of hypertension, CAD, HLD
• Mother Maryanne alive- 76 years old, history of dementia, osteoporosis 
• Brother Michael- alive, 57 years old, history of hypertension, CAD and cardiac stent placement (54 years old)
• Sister, Michelle- alive 53 years old, history of GERD, Asthma
• Brother- Jimmy- alive 50 years old, no past medical history

Social History: 

Mrs. B.C. works Monday-Friday 8am-5pm at the local dentist’s office at the front desk as a schedule coordinator. She is planning to retire in a few years. In her spare time, she is involved in various community efforts to feed the homeless and helps to prepare dinners at her local church one night a week. She also enjoys cooking and baking at home, gardening, and nature photography. 

Mrs. B.C. has two children. Her oldest son, Patrick, is 21 years old and is in his final year of pre-med. He is attending a public university about 2 hours away from home where he lives year-round. As an infant, Patrick was breastfed until 18 months when he self-weaned. Her daughter, Veronica, is 19 years old and lives at home while attending the local branch campus of a state university. She is in her second year of a business degree and then plans to transfer to the main campus next year. When Veronica was an infant she had difficulty latching onto the breast due to an undiagnosed tongue and lip ties resulting in Mrs. BC exclusively pumping and bottle feeding for six months. After six months, Mrs. B.C. was having a hard time keeping up while working and her found her supply diminished. Veronica had begun eating solid foods so Mrs. B.C. switched to supplemental formula, which was a big relief.

Mrs. B.C. was married to her now ex-husband Kent for 26 years. They divorced two years ago when Veronica was a senior in high school. They have remained friends and Kent lives 25 minutes away in a condo with his girlfriend. She also has two brothers who live nearby and a sister who lives out of state. Her 7 nieces and nephews range in age from 9 years old to 26 years old. Her father, George, passed away from a sudden stroke 4 years ago. Her mother, Maryanne, has dementia and is living in a nearby memory care facility. She also has many close friends. 

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Case report article, case report: young adults with breast cancer: a case series of fertility preservation management and literature review.

• 1 Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki, Japan
• 2 Department of Obstetrics and Gynaecology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
• 3 Laboratory of Cancer and Reproductive Science, Department of Frontier Medicine, St. Marianna University, School of Medicine, Kawasaki, Japan
• 4 Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan

Breast cancer comprised at least 21.8% of the overall cancer among young adult (YA) women and became the leading cancer in this group in Japan, with 50% adolescent and YAs being diagnosed and 15–44-year-old women showing excellent 5-year survival. Surgical-chemoradiation therapy often results in excellent survivorship with an increased incidence of treatment-induced subfertility. Therefore, adding fertility preservation (FP) to the primary cancer treatment is necessary. Herein, we reported a series of cases of YA women with breast cancer who opted for FP, where their option was tailored accordingly. To date, the selection of oocytes, embryos and ovarian tissue is widely available as an FP treatment. PGT could reduce the risk of BRCA mutation transmission amongst BRCA carriers before pregnancy planning. Otherwise, gonadotropin-releasing hormone analog has no gonadoprotective effect and thus should not be considered as an FP option.

Introduction

Breast cancer comprised at least 21.8% of the overall cancer among young adult (YA) women and became the leading cancer in this group in Japan, followed by cervical cancer at 12.8% and malignant germ cells and other gonadal tumors at 8.5% ( 1 ). Overall, 50% of breast cancer cases were among adolescent and YAs (AYA); in addition, the age group of 15–44 years old showed an excellent 5-year survival rate of almost 90% in localized cancer group, 80% in regional cancer group, and 35% in distant metastasis cancer group ( 2 ). The combination of surgical and chemoradiation therapy in managing breast cancer often results in excellent survivorship. However, it could also lead to a reduction in fecundity. Therefore, considering the increased incidence of chemotherapy-induced subfertility that leads to a devastating quality of life, adding fertility preservation (FP) to the primary cancer treatment is deemed essential in oncofertility services ( 3 ). A prompt strategy is paramount to evaluate FP's best option tailored to age, cancer stage age, and marital status. Herein, we reported a series of cases of YA women with breast cancer who opted for FP, where their option was tailored accordingly.

Case Series

Our first case is a 31-year-old single and nulliparous woman with newly diagnosed stage I of right breast cancer (T1N0M0). Her hormone receptors were found positive (ER+/PR+) with HERS2-ve and Ki67 < 10%. Therefore, she was planned for right mastectomy and sentinel axillary lymph nodes biopsy, followed by possible chemotherapy (Taxane-based group if the nodes were positive). She was also planned for tamoxifen (TAM) therapy for at least 10 years. Therefore, she was referred to us for FP with an interval of 10 weeks before operation intervention. Her level of anti-Mullerian hormone (AMH) was 4.51 ng/dL. Given that she was single with applicable timeframe, a choice of oocyte cryopreservation was deemed appropriate. She was keen to start controlled ovarian stimulation (COS) as soon as possible; thus, the random start (RS) protocol with an aromatase inhibitor (AI) was offered. She managed to cryopreserve 10 oocytes and is currently still ongoing second COS before embarking on surgery next month. Although the chemotherapy is not yet planned, she was referred for possible long-term endocrine therapy for 10 years. By the time of treatment completion, the AMH could decline due to aging. Given that she has a borderline AMH level, the prediction of a further decrease in AMH level made the FP essential in managing her condition. However, oocyte cryopreservation could help motivate compliance to the primary treatment disease as her fertility ability has been covered.

Our second case is a 28-year-old married woman with preliminary diagnosis of left breast cancer upon tissue biopsy. Unfortunately, her lymph nodes tissue was found to be positive. Thus, she was categorized as T2N1M0. However, her hormonal subtype was ER/PR+. HERS2 was also positive and Ki67 > 20% (luminar B-like tumor). She was counseled for a left mastectomy with unilateral axillary lymph node clearance, followed by chemotherapy; anthracycline-based group or combination with taxane-based regime depending on the final histopathology examination and immunochemistry assessment of post-surgical specimen. She was also counseled regarding the possibility of anti-HER2 therapy for 1 year, followed by TAM for at least 5 years. Her current AMH level was 2.32 ng/dL. Therefore, she was counseled for FP treatment because the chemotherapeutic agent is gonadotoxic and long-term therapy because she is married. The option of embryo cryopreservation was an excellent choice. The interval before the primary cancer treatment was 6 weeks. Thus, adequate time was available for her FP. Fortunately, she was on her second day of menses; thus, conventional COS was initiated. To date, she had eight embryos cryopreserved (blastocyst stage) following two cycles of conventional COS. She is currently receiving chemotherapy and was planned for years for a cryopreservation update. She responded well with the chemotherapy (doxorubicin + cyclophosphamide), and she is currently on trastuzumab. Her latest AMH was 0.08 ng/dL. She experienced amenorrhea after 6 months of chemotherapy. Due to the FP strategy, she secured her chance for pregnancy in the future despite having a poor ovarian reserve due to her primary cancer treatment.

Our third case is a 37-year-old single and nulliparous woman diagnosed with right breast cancer 6 years ago. She was referred to us previously for FP treatment. She was diagnosed as triple negative because all her hormonal receptors were negative. However, her BRCA status was unknown due to financial constraints for testing. Her AMH level was 3.18 ng/dL. The timeframe for stimulation was limited at that time as her chemotherapy was scheduled a week after the FP counseling. Thus, the ovarian tissue cryopreservation (OTC) opted to follow FP counseling. She underwent laparoscopic left oophorectomy for OTC in November 2013. We obtained 23 pieces of ovarian tissue (1 mm 3 per piece) and 13 MII oocytes after in-vitro maturation; both were cryopreserved. To date, she completed her chemotherapy (doxorubicin + cyclophosphamide and olaparib), and she is currently in remission. Her latest AMH was 0.96 ng/dL. Given that she is still single, she had no plan to fertilize the oocytes and continue follow-up yearly to update her cryopreservation status.

The last case is a 33-year-old nulliparous married woman with grade III intraductal carcinoma of the right breast, with ER/PR+, HERS2+, and Ki67 > 20%. Her current AMH level was 2.54 ng/dL. She was diagnosed in February 2018, and she underwent right mastectomy with ipsilateral axillary lymph node clearance a month later. She was referred to us within 6 weeks before the initiation of chemotherapy. We offered embryo cryopreservation but were only able to pursue a single COS cycle. She managed to preserve three good-quality embryos at that time (blastocyst stage). She received four cycles of doxorubicin and trastuzumab for 1 year and completed 3 years of TAM. Given that she is now in remission, she is keen to embark on pregnancy, with clearance obtained from her breast oncologist. She was planned for frozen embryo transfer (FET), with natural cycles for at least 3 months following the last dose of TAM as the “wash-out” period. Tentatively, her FET was planned for September 2021. Although the period was regular, her AMH level 6 months ago was 0.07 ng/dL, confirming the chemotherapy's gonadotoxic effect on her ovarian reserve. Thus, FP was an appropriate choice in her case.

All these cases represented the current scenario of managing breast cancer among YA women, where FP is deemed essential to be incorporated into the primary disease management. The gonadotoxic effect of the chemo-regime in breast cancer is contemplating, and recommendations seem to be inconclusive. Therefore, a proactive strategy in adding FP as a wise strategy in managing young women with breast cancer is appropriate. The summary of the cases is tabulated in Table 1 .

Table 1 . The summary of main characteristics and reproductive outcomes.

As known, at least 15–25% of breast cancer cases affected premenopausal women, with 7% below 40 years old, which is categorized as AYA group ( 3 ). This group usually has a poorer prognosis than the post-menopausal group. However, the surviving rate increased by up to 80–90% in locoregional type due to the efficient breast cancer treatment at present ( 2 , 3 ). At least 60% of the overall breast cancer among the AYA group is stage II, and above with highly associated with hormonal receptor-positive and high-grade variant. Thus, they highly likely require cytotoxic chemotherapy with prolonged endocrine therapy, which leads to low fecundity ( 4 ). Therefore, the FP treatment among AYA group is paramount. The types of cryopreservation among breast cancer varies in accordance with women's preference, marital status, and the availability of the interval timeframe for FP treatment, as suggested in the FP for breast cancer referral workflow ( Figure 1 ). Embryo cryopreservation is an established method worldwide ( 5 ). It is cost-effective and it reduces the interval of time for pregnancy because the embryo is ready to be transferred once pregnancy is desired. However, it is only permitted for women with a steady partner or those legally married, as elaborated in our second case. This treatment is the best choice among YA women as the majority had an established relationship in their life.

Figure 1 . The suggested referral work flow for oncofertility referral for breast cancer cases.

Oocyte cryopreservation is also recommended as the first line of treatment among single YA women, because it was no longer considered as experimental starting from 2013 ( 5 , 6 ). However, the number of oocytes is a key to determine the prediction of successful pregnancy concerning age. Among YA women, at least 15 oocytes are required to predict a 50% chance of successful pregnancy ( 6 ). Therefore, repeat COS is needed to ensure that a justified number of oocytes could be cryopreserved prior to chemotherapy. Likewise, in our first case, the patient already managed to secure 10 oocytes and continued to collect more oocytes in a given timeframe to ensure good pregnancy outcome in the future. Impromptu initiation of COS and its safety among breast cancer had been overcome by the implementation of random start (RS) protocol with a combination of AI in supplementing conventional COS. The usage of AI is well-known to stabilize the estradiol level to reduce the risk of activating estrogen-driven cancer cell ( 7 – 10 ). Meanwhile, the RS protocol helps overcome the delay in starting COS in the follicular phase, thus reducing the waiting time for FP treatment ( 10 , 11 ). Both of these measures have been proven as an effective strategy among cancer women without jeopardizing the numbers and quality of oocytes compared with conventional COS ( 8 ). Therefore, in our first case, we managed initiating the COS and RS-AI, and she successfully cryopreserved 10 oocytes. The subsequent cycles are still ongoing, with the aim of more oocytes to be cryopreserved.

OTC is not considered as the first line for YA women with breast cancer. It is usually reserved for women with limited timeframe, because FP treatment is squeezed prior to early chemotherapy schedule or in between ongoing chemotherapy cycle, thus making the combination of oocyte and embryo cryopreservation impossible. To date, OTC is still considered as experimental ( 12 – 14 ). The selection of OTC candidates is currently based on Edinburg's criteria to ensure a good outcome ( Table 2 ). Majority of the YA group who selected for FP treatment required cytotoxic chemotherapy, followed by long term hormonal suppression treatment, mainly TAM ( 1 , 11 , 12 ). By the time when ovarian tissue transplantation (OTT) is the aim, most of the women already had a low fertility potential due to the nature of the aging process. Fortunately, in women who received OTC, the possibility of harvesting immature oocytes simultaneously during the procedure could allow enhanced pregnancy outcome. The implementation of in-vitro maturation (IVM) made the maturation process possible, thus improving the FP outcome, because we managed to combine both oocytes and OTC ( 6 , 14 ). This scenario was reflected in our third case, where the patient received OTC due to the limited timeframe and managed to secure 13 oocytes via IVM during the procedure.

Table 2 . The Edinburg criteria for ovarian tissue cryopreservation ( 1 , 11 , 12 ).

By contrast, the implementation of gonadotropin-releasing hormone analog (GnRHa) as gonadal protection among women with breast cancer is still inconclusive ( 15 ). Most centers utilize it as a shield to reduce the direct effect of chemotherapy by creating a transient resting follicle environment. Theatrically, the resting follicles are more resistant to chemotherapeutic agents, thereby reducing the risk of ovarian damage. Surprisingly, most of the data concluded that the level of GnRHa suppression was not sufficient to protect the ovarian tissue from chemotherapeutic damage. Therefore, most of the international bodies do not recommend the usage of GnRHa as one of the FP strategies ( 15 , 16 ). Currently, GnRHa is mainly used to create the transient amenorrhea period to reduce the risk of heavy menstrual bleeding while on treatment compared with FP treatment. However, GnRHa is reserved as an FP option in centers where the established FP options, such as embryo, oocyte, or ovarian cryopreservation, were not available. Therefore, GnRHa was not offered for any of our cases ( 11 , 15 , 16 ).

Concerning germline mutation, at least 10% of young women with breast cancer were related to BRCA1 or BRCA2 gene. An increased risk of BC was seen in BRCA1 (20%) and BRCA2 (10%). Implementing these gene screenings has become an excellent strategy ( 17 ). However, they are still not widely available due to cost. Evidence did show that the BRCA-related BC ovarian reserve was lower than the non-BRCA BC ( 11 , 18 ). Therefore, FP should be offered before primary cancer treatment. The choice of FP should be carefully discussed as OTC may have the risk of reintroducing ovarian cancer (OC) following OTT. The risk of OC is 40% for BRCA1 compared to that for BRCA2 at 15% ( 17 ). Therefore, a lengthy discussion should be offered before OTC. Furthermore, following OTC, BRCA mutation BC has a lower number of oocytes per ovarian tissue piece than non-BRCA BC, leading to lower pregnancy chance following OTT. Thus, oocyte and embryo cryopreservation is considered as a better option in terms of inadequate FP timeframe for stimulation. The use of COS-AI is also recommended to reduce the risk of breast tissue stimulation ( 7 , 9 ). However, the risk of transferring to the offspring needs to be highlighted as an autosomal dominant (AD) link ( 17 , 18 ). It could be carried in cryopreserved oocytes or embryos. Thus, pre-implantation genetic testing (PGT) should be offered before embryo transfer or the usage of oocytes to determine the status of BRCA mutation ( 18 , 19 ). PGT could be a good FP strategy among BRCA BC women aiming for healthy offspring. The current limitation is the awareness and cost of testing that both lead to low uptake of FP among BRCA BC women. In our cases, none of the women was offered BRCA mutation screening due to cost, because it was not covered by insurance. As a proper FP strategy, BRCA mutation screening should be offered to young women with breast cancer to ensure good FP outcome.

In addition, most of the single women among breast cancer survivors in the YA group who received FP treatment have an increased possibility to remain single upon completion of the treatment ( 20 ). Therefore, the indefinite allowable duration of cryopreservation therapy and its effect on pregnancy outcome are still inconclusive. Previously published literature concluded that the duration of storage does not influence pregnancy outcome in cryopreserved material; thus, no timeframe was currently allocated for the duration of cryopreservation ( 21 ). The scenario is applicable to our first and third cases, as the cryopreservation will be renewed until they embark in a stable relationship and had a desire to conceive. Meanwhile, pregnancy in women with breast cancer was proven to be safe with no additional risk of recurrence with potentially more favorable prognosis compared with non-pregnant women with breast cancer ( 22 , 23 ). However, the timing of pregnancy is essential. To date, no evidence that recommends a proper timeframe from the diagnosis to pregnancy could be found. Most of the centers depend on the molecular subtype, histological grade, and stage of cancer when anticipating the risk of recurrence following pregnancy. The first 2–3 years is mostly vital to ensure no pregnancy due to an increased risk of recurrence, particularly in estrogen receptor-positive cases. Some of the centers tend to defer up to 5 years, especially in luminal-type and in women with positive lymph nodes, to ensure no late relapse ( 24 ). Regarding the subtype of BC with FP outcome, triple-negative BC was reported to have decreased oocyte yield and pregnancy rates ( 19 ). Therefore, the urgency of FP should be highlighted to this group to ensure that an adequate number of oocytes or embryos could be cryopreserved before chemotherapy. Our triple-negative case opted for OTC due to limited time for stimulation. Fortunately, with the IVM, she was able to secure 13 MII oocytes. Thus, the combination of OTC and OC improved her future fertility outcome.

In our center, we practice a conjoint decision with breast oncologist in determining the overall patient status before allowing pregnancy. On the basis of standard rules, most of our cases are considered for conception at least after 24 months of endocrine therapy with no evidence of relapse. Currently, our center is included in the clinical trial for “Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer” (The POSITIVE Trial, NCT02308085). This trial is recruiting women from the YA group with breast cancer who are willing to embark in pregnancy after receiving adjuvant endocrine therapy, either selective estrogen receptor modulator (SERM) alone or GnRHa + SERM or AI for ≥ 18 months but ≤ 30 months for early breast cancer ( 25 ). The study completed its first phase of recruitment and is now waiting for the analysis of the results. The estimated time for the completion of study recruitment is December 2028. Therefore, we allowed our fourth case to proceed with FET as she already finished the 2 years of TAM and deferred FET for at three 3 months following the last dose of TAM for “wash-out” period to ensure a good pregnancy outcome.

Management of breast cancer women in the YA group is complex, from the variant of molecular cancer subtype to the requirement of cytotoxic chemotherapy and desire for fertility. Therefore, a proper selection of cryopreservation type and targeted timeframe for pregnancy based on a joint decision from oncofertility specialist and breast oncologist is needed to facilitate the FP treatment. To date, the selection of oocytes, embryos, and ovarian tissue is widely available as an FP treatment. However, the risk of BRCA mutation transmission should be considered among BRCA BC women, and PGT should cooperate to ensure enhanced FP outcomes. GnRHa has no gonadoprotective effect and thus should not be considered as an FP option.

Data Availability Statement

The datasets presented in this article are not readily available because there are no data for this case series. Requests to access the datasets should be directed to nao@marianna-u.ac.jp .

Ethics Statement

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author Contributions

YS, MA, YS-T, and NS: conceptualization. YS, MA, YH-O, ST, SS, HI, ES, and YS-T: data curation. YS, MA, YH-O, YS-T, and ST: formal analysis. YS, MA, YH-O, YS-T, ST, and NS: methodology and project administration. YH-O, YS-T, ST, and NS: supervision. ES, MA, and YS-T: writing—original draft. YS, MA, YH-O, YS-T, ST, and NS: writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We would like to thank all the staff in reproductive outpatient clinic and reproductive center who contributed to this study.

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7. Cavagna F, Pontes A, Cavagna M, Dzik A, Donadio NF, Portela R, et al. Specific protocols of controlled ovarian stimulation for oocyte cryopreservation in breast cancer patients. Curr Oncol. (2018) 25:e527–32. doi: 10.3747/co.25.3889

8. Sfakianoudis K, Simopoulou M, Maziotis E, Giannelou P, Tsioulou P, Rapani A, et al. Evaluation of the second follicular wave phenomenon in natural cycle assisted reproduction: a key option for poor responders through luteal phase oocyte retrieval. Medicina. (2019) 55:1–14. doi: 10.3390/medicina55030068

9. Turan V, Bedoschi G, Emirdar V, Moy F, Oktay K. Ovarian stimulation in patients with cancer: impact of letrozole and BRCA mutations on fertility preservation cycle outcomes. Reprod Sci. (2018) 25:26–32. doi: 10.1177/1933719117728800

10. Wallace WH, Anderson RA, Irvine DS. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol. (2005) 6:209–18. doi: 10.1016/S1470-2045(05)70092-9

11. Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. (2018) 36:1994–2001. doi: 10.1200/JCO.2018.78.1914

12. Anderson RA, Baird DT. The development of ovarian tissue cryopreservation in Edinburgh: translation from a rodent model through validation in a large mammal and then into clinical practice. Acta Obstet Gynecol Scand. (2019) 98:545–9. doi: 10.1111/aogs.13560

13. Furui T, Takenaka M, Makino H, Terazawa K, Yamamoto A, Morishige KI. An evaluation of the Gifu Model in a trial for a new regional oncofertility network in Japan, focusing on its necessity and effects. Reprod Med Biol. (2016) 15:107–13. doi: 10.1007/s12522-015-0219-3

14. Marin L, Bedoschi G, Kawahara T, Oktay KH. History, evolution and current state of ovarian tissue auto-transplantation with cryopreserved tissue: a successful translational research journey from 1999 to 2020. Reprod Sci. (2020) 27:955–62. doi: 10.1007/s43032-019-00066-9

15. Abdel-Razeq H. Gonadotropin-releasing hormone agonists during chemotherapy for ovarian function and fertility preservation for patients with early-stage breast cancer. Cancer Manag Res. (2019) 11:4273–82. doi: 10.2147/CMAR.S204069

16. Bedoschi G, Turan V, Oktay K. Utility of GnRH-agonists for fertility preservation in women with operable breast cancer: is it protective? Curr Breast Cancer Rep. (2013) 5:302–8. doi: 10.1007/s12609-013-0123-y

17. Ghunaim S, Ghazeeri G, Khalife D, Azim HA Jr. Fertility preservation in patients with BRCA mutation. Ecancermedicalscience . (2020) 14:1033. doi: 10.3332/ecancer.2020.1033

18. Zhang X, Niu J, Che T, Zhu Y, Zhang H, Qu J. Fertility preservation in BRCA mutation carriers—efficacy and safety issues: a review. Reprod Biol Endocrinol. (2020) 18:11. doi: 10.1186/s12958-019-0561-0

19. Balayla J, Tulandi T, Buckett W, Holzer H, Steiner N, Shrem G, et al. Outcomes of ovarian stimulation and fertility preservation in breast cancer patients with different hormonal receptor profiles. J Assist Reprod Genet. (2020) 37:913–21. doi: 10.1007/s10815-020-01730-9

20. Carreira H, Williams R, Müller M, Harewood R, Stanway S, Bhaskaran K. Associations between breast cancer survivorship and adverse mental health outcomes: a systematic review. J Natl Cancer Inst. (2018) 110:1311–27. doi: 10.1093/jnci/djy177

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23. Pagani O, Partridge A, Korde L, Badve S, Bartlett J, Albain K, et al. Pregnancy after breast cancer: if you wish, ma'am. Breast Cancer Res Treat. (2011) 129:309–17. doi: 10.1007/s10549-011-1643-7

24. Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. (2007) 334:194. doi: 10.1136/bmj.39035.667176.55

25. Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer (POSITIVE) (2014–2021). Available from: https://clinicaltrials.gov/ct2/show/NCT02308085 (accessed July 1, 2021).

Keywords: breast cancer, cryopreservation, fertility preservation, oncofertility, young adult

Citation: Ahmad MF, Sugishita Y, Suzuki-Takahashi Y, Sawada S, Iwahata H, Shiraishi E, Takae S, Horage-Okutsu Y and Suzuki N (2021) Case Report: Young Adults With Breast Cancer: A Case Series of Fertility Preservation Management and Literature Review. Front. Med. 8:670872. doi: 10.3389/fmed.2021.670872

Received: 22 February 2021; Accepted: 13 July 2021; Published: 06 August 2021.

Reviewed by:

Copyright © 2021 Ahmad, Sugishita, Suzuki-Takahashi, Sawada, Iwahata, Shiraishi, Takae, Horage-Okutsu and Suzuki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Nao Suzuki, nao@marianna-u.ac.jp

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A Case of Locally Advanced Breast Cancer in a 59-Year-Old Man Requiring a Modified Approach to Management

Mohammed yousef aldossary.

1 Department of General Surgery, Surgical Oncology Unit, King Fahad Specialist Hospital, Dammam, Saudi Arabia

Fatimah Alquraish

2 Department of General Surgery, King Abdulaziz Air Base Hospital, Dhahran, Saudi Arabia

Jamila Alazhri

Patient: Male, 59

Final Diagnosis: Invasive ductal carcinoma

Symptoms: Foul-smelling discharge • painful breast mass

Medication: —

Clinical Procedure: Modified radical mastectomy

Specialty: Surgery

Rare disease

Background:

Male breast cancer is rare, accounting for approximately 1% of all malignancies in men. The lack of awareness of this rare cancer results in delayed diagnosis and its aggressive behavior can result in poor prognosis. This report is of a case of locally advanced, high-grade breast cancer in a 59-year-old man who was reluctant to undergo diagnostic procedures, and describes the approach to clinical management.

Case Report:

A 59-year-old man presented with a large left breast mass with enlarged axillary lymph nodes. The patient had ignored the mass and declined all diagnostic procedures. After modifying the diagnostic workup and involving a psychiatrist, the patient agreed to undergo a modified radical mastectomy. Histopathology showed a high-grade invasive ductal carcinoma with lymph node metastasis. The breast cancer was triple-positive for human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Adjuvant treatment included herceptin, tamoxifen, and radiation therapy.

Conclusions:

This case demonstrates the importance of raising public awareness of breast cancer in men, and to assess and overcome the factors leading to delay in accessing medical attention. In challenging cases, modifying the diagnostic workup and the treatment approach with the least deviation from the standard of care, including counseling may be required.

Worldwide, male breast cancer is extremely rare, accounting for <1% of all breast tumors and <1% of all malignancies in men [ 1 – 3 ]. Recently, the incidence of male breast cancer has increased from 1.0 per 100,000 men in the late 1970s to 1.2 per 100,000 men from 2000 to 2004 [ 4 – 7 ]. The American Cancer Society reported a similar trend in the incidence of breast cancer in men from 1975–1979 to 2010–2014 [ 7 , 8 ]. However, the prevalence of male breast cancer differs between countries, with Tanzania and areas of Central Africa reporting >6% of all breast cancers in men [ 9 ]. More than 40% of men with breast cancer present with advanced disease (stage III or IV) [ 10 ], resulting in a delay in diagnosis and treatment [ 11 – 14 ]. Assessing the factors that lead to delay in seeking medical attention is crucial to avoid delays in consultation and diagnosis and to prevent metastasis. The anatomy of the breast differs between men and women and because male breast cancer is so rare, the clinical guidelines for the diagnosis and treatment of breast cancer in men are based on those for women [ 1 ].

The clinical presentation of breast cancer in men caries from occult cancer with palpable axillary nodes to visible breast lumps with changes in the overlying skin [ 15 , 16 ]. Histologically, all breast types of breast cancer can occur in men, with invasive ductal carcinoma not otherwise specified (or ductal carcinoma NOS) being the most common [ 10 ]. The prevalence of psychological distress among patients with breast cancer is high, leading to a higher risk of depression, mood disorders, and anxiety [ 17 – 19 ]. Therefore, counseling is an important component of patient management before and after treatment. Treatment for locally advanced breast cancer includes neoadjuvant systemic therapy followed by surgery [ 20 ]. This treatment approach is indicated in breast cancer that is triple-negative, or for human epidermal growth factor receptor 2 (HER2)-positive breast cancer [ 21 , 22 ].

This report is of a case of locally advanced breast cancer in a 59-year-old man who was reluctant to undergo diagnostic procedures and describes the approach to clinical management.

Case Report

A 59-year-old man presented to the surgical clinic with discharge from a left breast mass. The mass had been increasing in size for more than one year. The patient described several attempts at cauterizing the left breast, without benefit. The patient did not seek medical care until he was in pain and developed foul-smelling discharge from the tumor. His only significant medical history was poorly controlled diabetes mellitus. The patient had received an elementary school education. He denied any history of psychiatric illness, the use of anabolic steroids, drug abuse, or alcohol consumption. He reported smoking about two packs of cigarettes each day for 30 years. There was no history of exposure to ionizing radiation or trauma. He had no family history of malignancy.

Clinical findings

The patient appeared to be generally well with a normal distribution of male body hair, no gynecomastia, and body mass index (BMI) of 36.9 kg/m 2 . Physical examination of the left breast and axilla showed a hard, erythematous, ulcerating, mass measuring approximately 9×5 cm in the subareolar region ( Figure 1 ). His left nipple was distorted by the mass with no discharge ( Figure 1 ). His body temperature was normal. Examination of the ipsilateral axilla showed an enlarged mobile lymph node. The right breast and axilla were normal on examination.

Preoperative photograph of the left breast of a 59-year-old man. An ulcerating large left breast mass is shown with distortion of the left nipple but with no discharge.

Laboratory investigations

Liver function tests showed the following results: albumin, 28 g/L; total protein, 48 g/L; alanine aminotransferase (ALT), 38 units/L; aspartate transaminase (AST), 42 units/L; alkaline phosphatase (ALP), 87 IU; total bilirubin, 5.9 µmol/L; conjugated bilirubin, 2.3 µmol/L; amylase, 56 units/L; and lipase, 37 units/L. All results were within their respective normal range. Tumor markers were also within the normal range: cancer antigen 19-9, 7 IU/mL; cancer antigen 15-3, 14.7 U/mL; prostate-specific antigen (PSA), 1.9 ng/mL; and carcinoembryonic antigen (CEA), 2.2 ng/mL. Other laboratory results were also unremarkable.

The patient refused core-needle biopsy or fine-needle aspiration cytology despite counseling regarding the importance of histopathological diagnosis and its impact on his treatment options, because of his fear of pain from these procedures.

Ultrasound examination of the breast and mammography were not feasible due to pain and discomfort in the left breast. The patient refused these imaging studies despite being prescribed strong pain medication. The patient did not comply with the recommendation for diagnostic workup for metastases in the form of computed tomography (CT) of the chest, abdomen, and pelvis, and a bone scan.

A psychiatric consultation was requested. The patient was diagnosed with an anxiety disorder. His major concern came from his belief that the biopsies or any contact with the breast mass during mammography or ultrasound examination might result in the spread of the disease and worsen his condition. He was treated with oral alprazolam 0.5 mg every six hours to relive his anxiety. Also, counseling and psychotherapy were provided. Eventually, the patient agreed only to undergo imaging without any contact between the equipment and his breast lesion. Computed tomography (CT) of the chest, abdomen, and pelvis showed a heterogeneous necrotic exophytic mass in the left breast associated with thickening of the skin. CT also showed an enhancing ipsilateral axillary lymph node with cortical thickening ( Figure 2A–2D ) and no distant metastases were identified. A bone scan did not identify bone metastases.

Computed tomography (CT) imaging of the left breast and axilla ( A ) Axial non-enhanced computed tomography (CT) imaging. ( B ) Axial enhanced computed tomography (CT) imaging shows a heterogeneous and necrotic exophytic mass in the left breast associated with thickening of the skin with a preserved fat plane between the mass and underlying pectoralis muscle. ( C ) Axial and ( D ) sagittal views show an enlarged ipsilateral axillary lymph node (arrows).

Although there was no preoperative diagnostic histopathology, the clinical presentation and the findings on CT scans were considered diagnostic for locally advanced breast cancer with metastasis to ipsilateral axillary lymph node. However, the lack of histological type, grade, and receptor status, precluded neoadjuvant chemotherapy as a treatment option and the patient was offered mastectomy. Axillary dissection was proposed as the treatment for axillary metastasis. The patient underwent a modified radical mastectomy. Intraoperatively, the mass was not found to be attached to the pectoralis major muscle. Level I and II axillary dissection was performed, the wound was closed primarily without the need for a skin graft.

Postoperative histopathology

The histopathology of the surgical resection specimen of the breast showed invasive ductal carcinoma with dermal deposits and lymphovascular invasion. The tumor was grade 3, measuring 8×8×6 cm. All surgical resection margins were free from tumor. Dissection of the axillary lymph nodes showed metastatic deposits in one of 19 lymph nodes ( Figure 3A, 3B ). Biomarker analysis using immunohistochemistry showed strong estrogen receptor (ER) positivity (70%,) progesterone receptor (PR) positivity (50%), and HER2 positivity (3+) ( Figure 4 ). The breast cancer was stage IIIB (pT4b, N1, M0).

Photomicrographs of the histopathology of the ductal carcinoma of the breast. ( A ) Histopathology shows a high-grade (grade 3) invasive ductal carcinoma. Hematoxylin and eosin (H&E). Magnification, ×10. ( B ) Histopathology shows intravascular emboli. Hematoxylin and eosin (H&E). Magnification, ×20.

Photomicrograph of the immunohistochemical staining of the ductal carcinoma of the breast for human epidermal growth factor receptor 2 (HER2). Immunohistochemistry shows strong HER2 positivity (3+) of the breast carcinoma cells (brown). Magnification, ×10.

Adjuvant treatment

The patient was referred to the medical oncologist and radiation oncologist for adjuvant treatment. Postoperative treatment with herceptin and pertuzumab was planned followed by adjuvant radiation therapy to the chest wall and axilla, and adjuvant tamoxifen for at least five years. The patient was also referred to a genetic counselor for BRCA gene mutation testing.

The American Cancer Society reported that the incidence of breast cancer in men increased from 1 per 100,000 men in 1975–1979 to 1.3 per 100,000 in 2010–2014 [ 7 , 8 ]. The number of new cases in the US was estimated to reach 2,550 in 2018, with patient mortality of 480 cases [ 7 , 8 ]. The mean age at diagnosis is 60–70 years [ 16 , 23 ], and the pattern of breast cancer in this age range tends to be similar to that in postmenopausal women [ 1 , 16 , 23 ]. However, cases have been reported in men as young as 10 years old [ 24 ]. While the risk factors for breast cancer in women are well-described, the risk factors for male breast cancer remain poorly understood due to its low incidence. However, Klinefelter’s syndrome is a possible risk factor for breast cancer in men, and other risk factors are similar to those for women, including acromegaly and neurofibromatosis [ 15 ]. In areas with a higher incidence of male breast cancer, including Central Africa and Eastern Africa, the etiology has been linked to hyperestrogenism resulting from endemic hepatic infection [ 25 ]. Supporting studies have confirmed that the combination of estrogen and progesterone is associated with an increased risk of breast cancer in postmenopausal women [ 26 , 27 ]. Breast cancer has also been reported in male to female transsexuals who use high doses of estrogen [ 28 ].

The delay in seeking medical attention will lead result in men presenting with advanced breast cancer. Al-Kahiry et al. [ 11 ] reported that 67% of their cohort of men with breast cancer presented with advanced disease. Clegg-Lamptey et al. reported that 57.6% of men presented with advanced stage breast cancer [ 29 ]. Bourhafour et al. [ 30 ] reported that 50.3% of male patients with breast cancer presented with stage III disease and 29% with stage IV breast cancer. Due to his late presentation, the patient in this report presented with stage IIIB locally advanced breast cancer that had already metastasized to the axillary lymph nodes. There are several factors that may lead to a delay in presentation, including lack of awareness about breast cancer, distance to the hospital, ignorance, fear of the consequences, a strong belief in traditional treatments, low educational level, ignorance, and poverty [ 13 , 31 – 35 ]. This patient had three factors that contributed to his late presentation, a strong belief in the benefits of traditional therapy, an elementary level of education, and being unaware of the condition.

The most common psychiatric co-morbidities in breast cancer patients are anxiety and depression [ 36 , 37 ]. Patients with breast cancer may experience anxiety and/or depression at any stage of the disease. Dastan and Buzlu [ 38 ] reported that 35% of female patients with breast cancer experienced anxiety. In this case, the support that the patient received from the psychiatrist, following his presentation to the hospital, encouraged him to cooperate to some extent with the clinical team. However, due to the late presentation, and the concern for disease progression, his psychotherapy session was brief.

The standard of care for the evaluation of patients with breast carcinoma is mammogram and ultrasound of the breast and axilla [ 20 ]. The strong misbelief that the patient had about the possibility of the spread of breast cancer from biopsy or contact with any equipment, initially prevented the standard diagnostic approach. However, due to the advanced tumor stage and the presence of a large ulcerating breast tumor and an enlarged ipsilateral axillary lymph node, and in addition to the clear requirement for mastectomy, mammography and ultrasound were not performed and computed tomography (CT) imaging was used, which showed the extent of the breast cancer and involvement of the axilla.

Invasive ductal carcinoma is the most common type of breast cancer in men [ 10 ]. Because the male breast is usually small, local and occult invasion by cancer cells tend to involve the pectoralis major. Mastectomy and radiotherapy is the recommended combined approach to achieve a complete tumor resection [ 39 ]. This patient did not have involvement of the pectoralis muscle on CT scan or by intra-operative clinical assessment. Histological assessment of the mastectomy specimen also showed negative deep margins.

Systemic treatment for breast cancer is determined by the hormonal and biological status of the tumor. A study by Avisar et al. [ 40 ] showed that 56% of cases of male breast cancer showed overexpression of HER2 [ 40 ]. This patient had a HER2-positive invasive ductal carcinoma of the breast (3+). In HER2-positive breast cancer, the standard of care is to start with herceptin-based neoadjuvant chemotherapy, which is associated with a 40% increase in the rate of pathological complete response [ 41 ]. Studies have shown that the inhibition of HER2 using the combination of herceptin and pertuzumab in the neoadjuvant setting can increase the complete response rate by 60% [ 42 – 44 ]. The longterm benefit of this treatment approach in terms of improved overall survival has also been shown [ 45 ]. However, this patient refused a preoperative diagnostic biopsy and it was not possible to identify the histological type of the tumor or the receptor status prior to surgery. Therefore, the treatment approach was changed for this patient and he was offered first-line surgical treatment followed by HER2-based chemotherapy in the adjuvant setting.

Conclusions

Male breast cancer is a rare but challenging malignancy for the clinician to manage, due to lack of patient awareness and the increased presentation at an advanced stage. Increasing public awareness of male breast cancer is essential to avoid the delay in clinical consultation, prevent axillary and distant metastases, and ensure diagnosis at a treatable stage. Assessing and modifying the factors that lead to a delay in seeking medical attention is crucial to improving patient prognosis. It is important for the treating physician to recognize the advantage of obtaining psychiatrist assistance as early as possible in the clinical management of patients with denial or who have misunderstandings of the condition, which may affect their ability to make decisions. In challenging scenarios, it is important for the treatment plan to be flexible to overcome difficult circumstances. As this case has shown, the diagnostic workup and the treatment approach can be safely modified with the least possible deviation from the standard of care guidelines to obtain the best outcome for the patient.

References:

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American Cancer Society launches long-term study to investigate racial disparities in breast cancer

100,000 black women needed for landmark cancer study.

Paula Tutman , Reporter

DETROIT – Cancer can impact absolutely anyone, yet it doesn’t affect everyone who gets it equally.

Black women are 40% more likely to die of breast cancer and under the age of 50, Black women are two times more likely to die of breast cancer than white women.

Why is that? The largest most comprehensive long-term study of its kind aims to answer these questions and many others. The American Cancer Society has begun a 30-year study to track and inform cancer treatment. The mammoth undertaking is looking for 100,000 Black women to participate.

The Voices of Black Women is mammoth in size, in scope and also in terms of how it can close disparity gaps when it comes to cancer and Black women.

When the American Cancer Society reaches its mark of 100,000 women, the deadline closes. In its first week, 1,000 women have already signed up. Data is already being collected and analyzed, but the strength of a study is in the numbers, so the sooner 100,000 women sign up, the sooner we’ll start seeing serious data patterns and information that could inform researchers and physicians.

More information -- including how to get involved -- can be found on the American Cancer Society website .

Copyright 2024 by WDIV ClickOnDetroit - All rights reserved.

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Paula tutman.

Paula Tutman is an Emmy award-winning journalist who came to Local 4 in 1992. She's married and the stepmother of three beautiful and brilliant daughters. Her personal philosophy in life, love and community is, "Do as much as you can possibly do, not as little as you can possibly get away with".

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May 20, 2024

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Study reveals promising development in cancer-fighting nanotechnologies

by Kat Gebauer, University of Oklahoma

A new study conducted by the Wilhelm Lab at the University of Oklahoma examines a promising development in biomedical nanoengineering. Published in Advanced Materials , the study explores new findings on the transportation of cancer nanomedicines into solid tumors.

A frequent misconception about many malignant solid tumors is that they are comprised only of cancerous cells . However, solid tumors also include healthy cells, such as immune cells and blood vessels. These blood vessels are nutrient transportation highways that tumors need to grow, but they can also be a pathway for medicine delivery, including for cancer nanomedicines.

Blood vessels, and the endothelial cells within them, are the transportation method examined in the new study led by Lin Wang, Ph.D., who was a postdoctoral research associate in the Wilhelm Lab while conducting the study and is the first author of the publication. Endothelial cells line blood vessels and manage the exchange between the bloodstream and surrounding tissues. These cells are the first barrier that the nanotechnologies encounter in the process of being transported into tumors.

The researchers found that endothelial cells in breast cancer tumors are two times more likely to interact with medicine-carrying nanoparticles than endothelial cells in healthy breast tissue. Wang said that the tumor endothelial cells have more transport features than the healthy endothelial cells, making them ideal conduits.

"If you know that the same cell type in tumor tissues is two times more likely to interact with your drug carriers than in healthy tissue, then in theory, you should be able to target those cells to get even more nanoparticles delivered into the tumor," said Stefan Wilhelm, Ph.D., associate professor in the Stephenson School of Biomedical Engineering and corresponding author of the study.

The research was conducted on endothelial cells isolated from breast cancer tissues and isolated from healthy breast tissues. The next steps for the research will involve examining how the nanoparticles react in the context of the whole tissue architecture.

"Cell-culture level experiments are only so good at trying to recapitulate what is happening in the body," said Wilhelm. "Working with colleagues at OU Health Sciences, we hope to get our hands on not just cells but the entire tumor tissue."

The research team is working with the Stephenson Cancer Center to set up an ethics protocol allowing the lab to access stored samples of cancer tissue rather than just isolated cells. The Wilhelm Lab is focused on studying nanomedicine and using nanoparticles for drug delivery and diagnostics. In particular, the team is interested in studying the delivery of drugs into solid tumor tissues.

From an engineering perspective, a unique advantage of using nanoparticles for drug delivery is that they are small and flexible enough to be designed as direct delivery vehicles. In a laboratory setting, the nanoparticles are often designed as tiny spheres and loaded with the necessary drugs. Then, in clinics, they are often administered intravenously to patients. These drugs circulate through the bloodstream, and some of them enter the tumor.

There are challenges associated with this type of medicine transportation. One is that these nanoparticles circulate throughout the body, and consequently, they accumulate in other organs—called off-target organs—such as the liver, spleen and kidneys. Since these organs filter blood, they remove the nanoparticles, which are often considered foreign objects by the body.

The field of nanomedicine has been around for more than 40 years, and there are tens of thousands of publications on using nanoparticles to treat cancers at the preclinical stage. But there is a disconnect between the number of preclinical publications and the number of FDA-approved formulations of nanoparticles that are actually used in clinics.

Of those approved formulations, a fraction are used for solid tumors, and most treat liquid tumors, such as leukemia. Wilhelm speculates that this is partially because there is a lack of full understanding of how the nanoparticle delivery process works.

"And if you don't understand something fully, it's hard to develop solutions to those problems," said Wilhelm.

"Researchers have started to go back to the fundamentals of nanomedicine development to understand the translation from the pre-clinical to the clinical space. Our lab wants to focus on these fundamentals to better understand the field and the delivery mechanisms specifically. If we understand these fundamentals, we can contribute even more to the field," said Wang.

According to Wilhelm, the next big question is this: now that the lab has quantified and shown that endothelial cells are more likely to interact with and transport these nanomedicines, how can that transportation be made more efficient and specific to advance clinical cancer treatments? As these questions are answered, the opportunities for future advances in cancer health care will grow.

"We are just scratching the surface by using breast cancer as our model cancer system, but our findings may be relevant for other types of solid tumors as well," said Wilhelm.

Journal information: Advanced Materials

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A new study, funded by the Prevent Breast Cancer charity, found breast tissue could be preserved in a special gel solution, enabling scientists to examine it in great detail.

Experts found the preserved breast tissue maintained its structure, cell types and ability to respond to a series of drugs in the same way as normal breast tissue.

The study, published in the Journal of Mammary Gland Biology and Neoplasia, could boost the development of new drugs to treat and prevent breast cancer, without the need for testing on animals.

Lester Barr, consultant breast surgeon and founder of Prevent Breast Cancer, said: “Breast cancer mortality is decreasing in the UK thanks to improved screening and treatment options, but incidences continue to rise and breast cancer is the most commonly diagnosed cancer in the UK.

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Researcher Hannah Harrison, of the University of Manchester, said: “There are various risk-reducing options for women at high risk of developing breast cancer - for example, those with a significant family history or who have mutations in the BRCA genes .

“However, not all drugs work for all women. This new approach means that we can start to determine which drugs will work for which women by measuring their impact on living tissue.

“Ultimately, this means that women can take the most effective drug for their particular genetic make up.

“By testing different hydrogel formulas we were able to find a solution that preserves human breast tissue for at least a week and often even longer.

“This is a real game-changer for breast cancer research in many ways.

“We can better test drugs for both the prevention and treatment of cancer, and can examine how factors like breast density - which we know is a risk factor for breast cancer - react to particular hormones or chemicals to see if this has an impact on cancer development.”

Scientists used the gel solution VitroGel to preserve the tissue.

In their work, they said the identification of new drugs has been previously “hampered by a lack of good pre-clinical models”.

What has been available until now cannot “fully recapitulate the complexities of the human tissue, lacking human extracellular matrix, stroma, and immune cells, all of which are known to influence therapy response”, they said.

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• Published: 18 May 2024

Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study

• Yi Wang 1 ,
• Yibo He 1 ,
• Shiyan Wu 1 &
• Shangnao Xie 1  

Scientific Reports volume  14 , Article number:  11364 ( 2024 ) Cite this article

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• Breast cancer
• Quality of life

To determine the impact of breast conservation on quality of life and identify treatment-related and other demographic factors associated with post-breast cancer treatment quality of life. A prospective study was conducted on 392 women who underwent breast cancer surgery at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022. Operable breast cancer patients who had completed all treatments except endocrine therapy were included. Patients with tumor recurrence/metastasis, bilateral or male breast cancer, and other primary malignancies were excluded. After enrollment, patients were asked to complete the BREAST-Q scale, and their pathological and medical records were reviewed. Analysis of variance was used to compare the quality of life scores among the groups. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with quality of life scores in different domains. Participants completed the BREAST-Q scale at a median of 4.6 years after surgery. Quality of life scores varied based on the therapeutic strategy. Breast conservation has significant advantages over mastectomy in terms of breast satisfaction, psychosocial, and sexual well-being. Compared to oncoplastic breast-conserving surgery, mastectomy was independently associated with decreased breast satisfaction, psychosocial, and sexual well-being, while conventional breast-conserving surgery showed comparable outcomes to oncoplastic breast-conserving surgery in terms of these factors. Breast conservation leads to an improvement in quality of life compared to mastectomy. Oncoplastic breast-conserving surgery does not lead to a decrease in quality of life compared to conventional breast-conserving surgery and offers better outcomes compared to mastectomy.

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Introduction.

Breast cancer is a prevalent global malignancy 1 , and breast-conserving surgery (BCS) with adjuvant radiotherapy (RT) is a well-established treatment for early-stage breast cancer 2 , 3 . However, up to 30% of BCS recipients express dissatisfaction with their postoperative appearance, necessitating corrective interventions 4 . In the 1980s, European surgeons introduced "oncoplastic breast-conserving surgery" (OBCS), which incorporates plastic surgery techniques for post-BCS breast defect reconstruction 5 .

While OBCS offers satisfactory long-term oncological results and broadens treatment possibilities for patients who would typically undergo mastectomies 6 , it involves more extensive incisions, additional tissue manipulation, and potential flap reconstruction in comparison to conventional breast-conserving surgery (cBCS) 7 , 8 . The procedures involved in OBCS are more complex, time-consuming, and costly. Given these complexities, is it still worthwhile to pursue breast conservation by OBCS? Some researchers have proposed whether the use of OBCS should be reduced 9 .

Understanding the impact on the quality of life of breast cancer survivors is crucial given its significant influence on medical decision-making 10 , 11 . Despite the widespread utilization of OBCS to conserve the breast and enhance its aesthetics, research on its impact on quality of life is limited and complicated due to the variability of surgical approaches. Consequently, this study aimed to assess the effect of breast conservation by OBCS on the quality of life of patients with operable breast cancer treated at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022, and to elucidate the treatment and demographic factors associated with postoperative quality of life.

Materials and methods

This prospective, cross-sectional, case–control study was conducted at a single center. The inclusion criteria were operable breast cancer patients treated at Hangzhou Cancer Hospital between January 1, 2013, and December 31, 2022, who had completed all treatments except endocrine therapy and provided participation consent. The exclusion criteria were patients with tumor recurrence/metastasis, bilateral or male breast cancer, or other primary malignancies. Participants were categorized into two groups: BCS group (cBCS with RT subgroup and OBCS with RT subgroup), and unilateral MAST group (MAST with RT subgroup and MAST without RT subgroup). This study utilized the BREAST-Q scale 12 , which includes separate modules for BCS and MAST without reconstruction. The BCS module was used for the OBCS with RT subgroup because OBCS in this study predominantly referred to oncoplastic lumpectomy/glandular remodeling. BREAST-Q assesses six distinct domains: satisfaction with breasts, psychosocial well-being, physical well-being, sexual well-being, satisfaction with overall outcome, and satisfaction with care. Due to the elapsed time between surgery and questionnaire completion in this study, the domains of satisfaction with the overall outcome and satisfaction with care were excluded. Each domain was scored on a scale from 0 to 100, with higher scores indicating an enhanced quality of life. Differences in BREAST-Q scores were categorized as small (2–3 points), moderate (4–7 points), and large (8–10 points) 13 . Patient characteristics, collected using the questionnaire, included employment status, educational level, marital status, and economic status. Patients’ medical and pathological records were reviewed to determine the disease tumor, node, and metastasis (TNM) staging 14 , erythroblastic oncogene B (ERBB2; formerly HER2/neu or HER2) status, hormone receptor status, and body mass index (BMI). Information on surgery, chemotherapy (yes/no), RT, and endocrine therapy (yes/no) was obtained using a questionnaire in conjunction with medical records. The lymphedema status (yes/no) was assessed using the questionnaire's question regarding arm swelling. This study was approved by the Ethics Committee of Hangzhou Cancer Hospital, and all participants provided written informed consent. The study was performed in accordance with the Declaration of Helsinki and followed the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) reporting guidelines.

Statistical analysis

The experimental data were statistically analyzed using SPSS (version 29.0) software, and categorical covariates were expressed as numbers (percentages). Analysis of variance (ANOVA) was used to compare quality of life scores among the different groups. Univariate and multivariate linear regression analyses were used to determine the independent factors associated with the quality of life scores in each domain. Variables with two-tailed P  ≤ 0.15 in the univariate analysis were included in the multivariate analysis model using a stepwise method to establish the final multivariate model. Differences with P  < 0.05 were considered statistically significant.

Ethics approval and consent to participate

This study was reviewed and approved by the ethics committee of Hangzhou Cancer Hospital (approval number: [hzch-2023] HS no.007). Written informed consent was obtained from every patient.

Patient enrollment

After screening, 623 eligible patients were invited, 456 provided written informed consent and completed the survey, but three were found to not meet the inclusion criteria after enrollment. After excluding 61 participants who only completed a brief questionnaire, a total of 392 patients’ data were included in the statistical analysis.

Patient, disease, and treatment characteristics

The interval between surgery and scale completion averaged 4.6 years (range: 0.33 to 9.83 years). Patient characteristics are detailed in Table 1 . Majority were married, employed, had moderate economic status (income ¥30,000–200,000 per year), and high school or higher education. At surgery, 324 (82.7%) patients had a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) within the normal range (18.5 to 23.9 kg/m 2 ), and 56 (14.3%) patients had a BMI of 24 kg/m 2 or above. Among the patients, 39 (9.9%) had stage 0 breast cancer, 154 (39.3%) had stage I breast cancer, 158 (40.3%) had stage II breast cancer, and 41 (10.5%) had stage III breast cancer. The lesions on imaging before surgery of 253 (64.5%) patients measured two centimeters or less, 134 (34.2%) two to five centimeters, and 5 (1.3%) more than five centimeters. Chemotherapy was administered to 293 (74.7%) patients, with 121(30.9%) receiving neoadjuvant chemotherapy, and 273 (69.6%) patients received hormone therapy.

Treatment details including surgery, RT, and lymphedema are presented in Table 1 . Among the patients, 88 (22.4%) underwent OBCS, 51 (13.0%) underwent cBCS, and 253 (64.5%) underwent unilateral MAST, among which 100 (25.5%) patients who underwent unilateral MAST received postoperative RT. All patients underwent axillary surgery, with 255 (65.1%) patients undergoing sentinel lymph node biopsy only and 137 (34.9%) patients undergoing axillary lymph node dissection. 61 (15.6%) patients reported having lymphedema.

BREAST-Q results by breast surgery strategy

Figure  1 illustrates unadjusted mean BREAST-Q scores by breast surgery strategy. Satisfaction with breasts, psychosocial well-being and sexual well-being were significantly different among the groups ( P  < 0.001). BCS group showed higher scores in satisfaction with breasts (61.70), psychosocial well-being (76.01), physical well-being (83.52) and sexual well-being (55.06), while the scores for MAST group is lower (satisfaction with breasts: 57.30, psychosocial well-being: 70.83, physical well-being: 82.40 and sexual well-being: 49.21).

Unadjusted BREAST-Q mean scores by breast surgery strategy. BCS: breast-conserving surgery; MAST: mastectomy.

Satisfaction with breasts

Higher scores in satisfaction with breasts correlated independently with age ≥ 60 (β = 4.662; 95% CI = 2.345 to 6.979; P  < 0.001) and patient-reported income ≥ 200,000 (β = 5.068; 95% CI = 2.781 to 7.356; P  < 0.001). Lower scores were associated with BMI ≥ 24 (β = − 2.528; 95% CI = − 4.977 to − 0.079; P  = 0.043), axillary dissection (β = − 4.875; 95% CI = − 6.704 to − 3.046; P  < 0.001) and MAST (β = − 3.927; 95% CI = − 5.741 to − 2.113; P  < 0.001) (Fig.  2 A). Patient-reported income < 30,000 and lymphedema showed significance only in univariate analysis. Other factors exhibited no significant association.

Patient and treatment factors associated with breast satisfaction ( A ), psychosocial well-being ( B ), physical well-being ( C ) and sexual well-being ( D ) scores by breast surgery strategy. MAST: mastectomy; BCS: breast-conserving surgery; BMI: body mass index; CI: confidence interval.

Psychosocial well-being

Better psychosocial well-being correlated with age ≥ 60 (β = 2.564; 95% CI = 0.163 to 4.965; P  = 0.036), patient-reported income ≥ 200,000 (β = 4.820; 95% CI = 2.496 to 7.144; P  < 0.001), and ≥ 5y from surgery (β = 2.419; 95% CI = 0.523 to 4.315; P  = 0.013). Poor psychosocial well-being was linked to age < 35 (β = − 3.892; 95% CI = − 7.715 to − 0.069; P  = 0.046), BMI ≥ 24 (β = − 3.352; 95% CI = − 5.845 to − 0.859; P  = 0.009), patient-reported income < 30,000 (β = − 4.489; 95% CI = − 7.317 to − 1.660; P  = 0.002), axillary dissection (β = − 5.898; 95% CI = − 7.739 to − 4.058; P  < 0.001) and MAST (β = − 5.157; 95% CI = − 7.032 to − 3.283; P  < 0.001) (Fig.  2 B). Chemotherapy was only significant in univariate analysis. Other variables showed no significant association.

Physical well-being

Factors associated with better physical well-being were age ≥ 60 (β = 3.594; 95% CI = 1.554 to 5.634; P  = 0.001), patient-reported income ≥ 200,000 (β = 4.541; 95% CI = 2.559 to 6.524; P  < 0.001), and ≥ 5y from surgery (β = 2.311; 95% CI = 0.714 to 3.907; P  = 0.005). Conversely, patient-reported income < 30,000 (β = − 5.924; 95% CI = − 8.351 to − 3.497; P  < 0.001), axillary dissection (β = − 2.486; 95% CI = − 4.057 to − 0.914; P  = 0.002) and lymphedema (β = − 2.185; 95% CI = − 4.275 to − 0.094; P  = 0.041) were associated with poorer physical well-being (Fig.  2 C). < 1y from surgery was only significant in univariate analysis. Other factors lacked significant association.

Sexual well-being

Multivariate analysis indicated lower sexual well-being scores with BMI ≥ 24 (β = − 2.887; 95% CI = − 4.831 to − 0.943; P  = 0.004), < 1y from surgery (β = − 3.482; 95% CI = − 5.887 to − 1.077; P  = 0.005), axillary dissection (β = − 3.002; 95% CI = − 4.437 to − 1.567; P  < 0.001), and MAST (β = − 5.650; 95% CI = − 7.114 to − 4.187; P  < 0.001). Patient-reported income ≥ 200,000 (β = 2.272; 95% CI = 0.441 to 4.104; P  = 0.015) correlated with elevated sexual well-being (Fig.  2 D). Lymphedema was significant in univariate analysis. Other variables exhibited no significant correlation.

BREAST-Q results by local therapy strategy

To assess if there were enhancements in quality of life among women who underwent OBCS, we performed similar analyses among the subgroups. Figure  3 illustrates unadjusted mean BREAST-Q scores by local therapy strategy. All four domains were significantly different ( P  < 0.05). OBCS with RT group showed highest scores in satisfaction with breasts (61.99), psychosocial well-being (76.27) and sexual well-being (55.53). cBCS with RT group yielded the highest physical well-being score (84.10). The lowest domain scores were in MAST with RT group (satisfaction with breasts: 53.11, psychosocial well-being: 65.49, physical well-being: 79.89 and sexual well-being: 46.24).

Unadjusted BREAST-Q mean scores by local therapy strategy. RT: radiotherapy; cBCS: conventional breast-conserving surgery; OBCS: oncoplastic breast-conserving surgery; MAST: mastectomy.

Multivariate analysis indicated that MAST with RT was associated with poor breast satisfaction (β = − 8.381; 95% CI = − 10.858 to − 5.905; P  < 0.001), psychosocial well-being (β = − 11.491; 95% CI = − 14.039 to − 8.943; P  < 0.001), physical well-being (β = − 3.607; 95% CI = − 5.782 to − 1.432; P  = 0.001) and sexual well-being (β = − 9.493; 95% CI = − 11.454 to − 7.533; P  < 0.001). MAST without RT was associated with decreased breast satisfaction (β = − 2.536; 95% CI = − 4.817 to − 0.255; P  = 0.029), psychosocial well-being (β = − 3.171; 95% CI = − 5.487 to − 0.855; P  = 0.007) and sexual well-being (β = − 4.739; 95% CI = − 6.530 to − 2.947; P  < 0.001). cBCS with RT was not associated with BREAST-Q scores on univariate or multivariate analysis. The statistically significant factors correlated with BREAST-Q scores were mostly consistent with the outcomes of the breast surgery models (Fig.  4 ).

Patient and treatment factors associated with breast satisfaction ( A ), psychosocial well-being ( B ), physical well-being ( C ) and sexual well-being ( D ) scores by local therapy strategy. cBCS: conventional breast-conserving surgery; OBCS: oncoplastic breast-conserving surgery; MAST: mastectomy; RT: radiotherapy; BMI: body mass index; CI: confidence interval.

The rates of BCS and breast reconstruction after mastectomy are significantly lower in China than in Western countries 15 . One contributing factor is that Chinese women typically have smaller breast sizes than women in Western countries, while presenting with larger breast tumor volumes at the time of initial diagnosis, making BCS challenging. Additionally, some Chinese patients adhere to outdated beliefs and have concerns about potential impacts on treatment outcomes or cancer recurrence associated with BCS. OBCS provides acceptable long-term oncological outcomes and has extended treatment options for patients who would traditionally be candidates for mastectomies 6 . In recent years, there has been a clear change in the emphasis of surgical oncology in China, with a growing emphasis on utilizing modern oncoplastic surgical techniques to perform more breast conserving surgeries. Given the increasing prevalence of OBCS, it is essential to examine its impact on quality of life.

In this single-center prospective study, discernible disparities in quality of life surfaced among patients with breast cancer undergoing various local treatment strategies within ten years of surgery. Patients opting for more extensive surgery, particularly when combined with RT, experienced diminished quality of life; satisfaction with breasts; and psychosocial, physical, and sexual well-being. This aligns with findings from prior studies. Engel et al.’s study 16 has shown that patients undergoing BCS reports a higher quality of life compared to those opting for mastectomy. This improvement is often linked to the conservation of the breast and the associated psychological advantages. BCS enables breast conservation, leading to enhanced body image and self-esteem. Patients undergoing BCS may experience less psychological distress and enjoy better psychosocial well-being due to breast conservation. Additionally, BCS has a lesser impact on sexual well-being in comparison to mastectomy, as it retains natural breast tissue.

This study’s findings concur with those of Otsuka et al.’s study 17 in that oncoplastic surgery improved satisfaction with breasts. However, in Otsuka et al.’s study, the quality of life score was not elevated by OBCS (major breast surgery: 154.5 ± 24.6; minor breast surgery: 159.0 ± 20.8; OBCS: 158.7 ± 14.0). Although differences exist between major breast surgery and OBCS, the difference is not pronounced. In the present study, psychosocial and sexual well-being scores were elevated compared to MAST. Additionally, patients who underwent OBCS had better physical well-being scores than those who underwent MAST with RT and equal physical well-being scores than those who underwent MAST without RT. This may be attributable to the omission of RT, reduced chemotherapy and lymphedema in the MAST without RT group. Previous studies 18 , 19 have highlighted RT, chemotherapy, and lymphedema as adverse determinants of quality of life.

Rose et al. 20 suggested that patients who underwent OBCS showed significant improvement in the “psychosocial well-being” module compared to cBCS, while no significant differences were observed between the two groups in the “physical health,” “breast satisfaction,” and “sexual health” modules. Furthermore, a meta-analysis 21 indicated improved quality of life with OBCS compared with cBCS in patients with early-stage breast cancer, with better physical and psychological well-being, higher self-esteem, and a more stable body image, leading to improved social and emotional functioning. However, the clinical studies included in the meta-analysis were predominantly small- sample studies from single centers, and the surgical approaches varied. This study identified no significant differences in any of the quality of life modules between the patients who underwent OBCS and those who underwent cBCS, which is consistent with the findings of de Oliveira-Junior et al 22 . This may be because the present study’s follow-up time was longer, and several aspects of OBCS will decline over time 23 . In our study, the tumor lesion on imaging before surgery averaged 2.11 ± 0.67 cm in OBCS subgroup, and 1.62 ± 0.52 cm in cBCS subgroup. Smaller lesions are more likely to undergo cBCS, resulting in comparable cosmetic outcomes between the two surgical groups. Moreover, the limited number of BCS patients in our study is a significant factor that limits the ability to detect differences in quality of life between OBCS and cBCS subgroups.

In addition to the type of surgery, other clinical factors such as BMI (≥ 24), income (< 30,000), < 1y from surgery, axillary dissection, and lymphedema were negatively correlated with quality of life. Identifying these risk factors can facilitate early postoperative intervention and ultimately improve the postoperative quality of life of patients with breast cancer. Age (≥ 60) and ≥ 5y from surgery were associated with enhanced quality of life. Breast cancer patients can experience significant effects from the disease itself and the ongoing adjuvant therapies, both after diagnosis and during the treatment process 24 . These are all factors that lead to decreased quality of life within 5 years, especially within 1 year, rather than ≥ 5y after surgery. Moreover, good economic status was associated with better satisfaction with breasts, and psychosocial, physical, and sexual well-being. Patients with improved financial circumstances can access higher-quality healthcare services, opt for more expensive treatment options that may improve aesthetic outcomes. The financial advantage also affords patients more opportunities for supportive care, counseling, and resources to manage the challenges of breast cancer treatment and recovery, resulting in a decrease in stress, anxiety, and depression. These enhancements can have a positive impact on patients’ self-perception, confidence, and overall satisfaction with their breast appearance, all of which are closely connected to sexual health and intimacy. Notably, other studies 25 , 26 found an association between economic status and quality of life.

This study has some limitations. It was a cross-sectional, single-time, survey-based prospective study; therefore, the baseline quality of life of patients before surgery was not recorded, which may have influenced their choice of surgical approach and postoperative quality of life. Additionally, this study did not identify patients who chose MAST due to refusal of BCS; patients who selected MAST based on personal preferences may have different quality-of-life scores. Furthermore, this study did not include patients with postmastectomy breast reconstructions, which may improve quality of life of postmastectomy patients. Finally, given that this was a single-center small-sample study, studies with larger sample sizes are required to further confirm the findings of this study. Nevertheless, patient-reported questionnaires can provide basic information on quality of life and assist in identifying potential areas requiring intervention during the patient’s survival period.

OBCS is an acceptable option for patients with larger tumors who are not suitable for cBCS because it allows them to conserve their breasts 6 . This study demonstrated that patients who had their breast conserved reported a higher quality of life compared to mastectomy patients. Despite extensive incisions, additional tissue manipulation, and potential flap reconstruction, patients who underwent OBCS did not report a lower quality of life than those who underwent cBCS. Furthermore, they experienced significantly enhanced quality of life compared with patients who underwent MAST, particularly in the domains of satisfaction with breasts, psychosocial well-being, and sexual well-being. Quality of life data should be incorporated into decision support tools to assist patients with breast cancer in selecting the surgical approach, and discussions with patients should include information regarding quality of life to ensure that they understand the long-term impacts of different surgical approaches. This is particularly crucial because most patients with breast cancer have an extended postoperative survival period. Our data can support further improvements in Chinese breast surgical care for better survival and quality of life.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to Chinese law but are available from the corresponding author on reasonable request.

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The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the Hangzhou Cancer Hospital is intended nor should be inferred.

This research was financed by the Medical and Health Research Project of Zhejiang Province, China (No. 2023KY964).

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Division of Breast Surgery, Department of Surgical Oncology, Hangzhou Cancer Hospital, Zhejiang, China

Yi Wang, Yibo He, Shiyan Wu & Shangnao Xie

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YW and SX contributed to the conception, design, wrote the manuscript and analyzed the data; YH was responsible for the execution and for data collection; and SW supervised the study. All authors read and approved the final manuscript.

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Correspondence to Shangnao Xie .

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Wang, Y., He, Y., Wu, S. et al. Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study. Sci Rep 14 , 11364 (2024). https://doi.org/10.1038/s41598-024-62105-z

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Received : 05 October 2023

Accepted : 14 May 2024

Published : 18 May 2024

DOI : https://doi.org/10.1038/s41598-024-62105-z

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