I’m happy to present to you this month, “On the Spot” debates on breast cancer and mastectomy, and specifically surgical resection of the primary tumor for women with metastatic breast cancer, timing of sentinel lymph node (SLN) biopsy, timing of radiation with respect to breast reconstruction, nipple-sparing mastectomy, and gene patenting and the exclusive right to perform clinical tests or research.
You’ve heard these experts at the podium, you’ve read their journal articles, but now you get to hear them talk candidly. Once you’ve read what they have to say, look at your own practices and experience and see how their arguments measure up. Then it’s up to you to determine your own stance, which we’d love you to share with us.
Your opinions are an important piece of the puzzle.
Thank you to this month’s contributors for their candid responses and for the time it took to share them. Please feel free to email me at email@example.com with any ideas for debate on breast cancer and other areas of clinical oncology, thoughts on this month’s column or general feedback, and comment online as well. I always like hearing from you!
Ms. Hutchinson is a medical communications consultant based in Philadelphia.
Statement:For the 10% of patients who have breast cancer metastasis at the time of diagnosis, some would say there is tremendous uncertainty and a lack of information regarding definitive treatments in terms of removing the tumor from the breast—for example, does tumor removal improve long-term outcome or is mortality dictated by metastasis? In these patients, the preferred option is to immediately operate versus the watch-and-wait approach of deferring surgery and seeing how the patient does on systemic therapy.
Cassann Blake, MD: Agree. Studies have shown that removal of the primary breast cancer either has no impact on survival or improves survival. Given that surgery to remove the primary tumor is a low-morbidity procedure and does not worsen survival, it is a reasonable discussion to have with stage IV breast cancer patients. My preferred approach is watch and wait to see how the patient responds to systemic therapy, which offers the logical first course of therapy to temporize progression of metastatic disease. Mortality in stage IV breast cancer could be a multifactorial process that, for some patients, involves the status of the primary breast cancer if they have shown a response to systemic therapy. It is hopeful that robust accrual to the ECOG-E2108 trial (Phase III Randomized Study of Early Local Therapy Comprising Surgery versus Standard Palliative Therapy for the Intact Primary Tumor in Patients with Stage IV Breast Cancer) will provide definitive results to guide multidisciplinary breast teams on who would best benefit from local therapy in the metastatic setting.
Larry Norton, MD: On the fence. Right now, pending clinical trial data, I would say that it depends on the situation, in particular whether the local disease or the metastatic disease is most threatening to life and/or quality of life. And indeed, we do not know if local surgical therapy is indicated at all in such cases. From a theoretical point of view, arguments can be made either way, so it is critical that we address these issues in the context of clinical trials that also assess biomarkers.
Tari King, MD: Disagree. New insights into cancer biology have resulted in a shift in our approach to systemic treatment for breast cancer, with an increased focus on biologic subtypes and targeted therapy. Given the documentation of improved survival for women with stage IV breast cancer and the anticipation that survival for this group will continue to improve with newer targeted systemic agents, the question of whether or not surgery for the primary tumor impacts survival in this setting is increasingly important. At last count, at least 19 retrospective studies have addressed this question, with the majority concluding that surgery, or local therapy with radiation, is associated with improved survival. Although all of these studies are inherently biased by their retrospective nature, the consistency of the results has led to the opening of five prospective randomized trials designed to definitively answer the question of whether local-regional treatment can further improve outcomes for patients with metastatic disease. Two of these trials (Turkish and Danish groups) randomize patients to surgery or no surgery prior to systemic therapy and the other three trials, including the U.S. trial (ECOG), randomize patients after assessing response to primary systemic therapy. If the tumor functions as a source of new metastatic deposits, treating it early in the course would intuitively seem to have greater benefit, yet the retrospective studies examining the timing of surgery are very limited and the results are inconsistent. Given the lack of level 1 evidence that surgery—at any time—improves survival, in my opinion the preferred option is to encourage patients to enroll in prospective trials so that we can definitively answer this important question.
Mary Jane Houlihan, MD: On the fence. Most women who present with stage IV disease will die of their disease within 24 to 30 months, and in most women, there is little to no role for mastectomy. However, there is a small subset of women with limited metastatic disease who are young, healthy and have a primary tumor that is completely resectable, who would benefit from mastectomy and axillary surgery as part of a multidisciplinary approach. For these women, it is unlikely that we are curing them; however, their life expectancy may be prolonged.
Mehran Habibi, MD: I agree with surgery in the setting of oligometastatic disease. There is no prospective randomized study reported on this to date. We are currently part of a multicenter study looking into this subject, but the recruitment is slow because of patient self-selection bias. It means that if the patients who are presenting with the metastatic breast cancer are responding to the medical therapy or having a stable disease, most of them opt to have the surgery on the breast lesion. Retrospective and animal studies as well as in other tumors may suggest that removing the index tumor may have a positive effect on the immune system and help with the cancer therapy. I usually offer surgery to patients with breast cancer and oligometastatic disease or those with good response to the systemic therapy.
Marisa Weiss, MD: Disagree. Systemic therapy is the mainstay of treatment for metastatic disease, as it’s the only form of therapy that addresses all areas of tumor involvement. Interval symptomatic and imaging re-evaluation are done to monitor response. Surgery has a limited role.
Grant Carlson, MD: Agree. Approximately 5% of women with breast cancer will present with systemic metastases at diagnosis. Modern systemic therapy has markedly improved survival in patients with systemic disease. Local treatment in this setting is controversial and is currently being examined in randomized trials. Meta-analysis of retrospective reviews has shown a significant survival benefit for treating the primary cancer independent of age, tumor extent and site of metastatic disease. There are several possible mechanisms why removing the primary would affect survival. Surgical treatment of the primary may reduce the patient’s tumor burden and reduce the levels of circulating tumor cells. The primary tumor may have immunosuppressive effects that can be reversed by removal. Local control can also significantly impact quality of life. I prefer for patients in this setting to be treated with systemic therapy and wait a period of time to assess primary tumor response prior to local treatment. In patients with large ulcerative tumors that are resectable, I prefer local treatment at the onset.
Seema Khan, MD: Disagree. The existing literature supporting surgical resection of the primary tumor for women with metastatic breast cancer is entirely retrospective and biased. Several trials are ongoing worldwide (including ECOG 2018 in the U.S. and Canada), and practitioners who have access to a trial should offer such a patient, trial participation. Outside of a trial, immediate surgery still does not make sense, since there is little chance that a tumor that does not respond to distant sites will behave differently if the primary site is resected. Therefore, the only logical plan requires initial systemic therapy for distant disease; this will also lead to a response at the primary site in the majority of cases and will avoid a delay in the initiation of systemic therapy, with its proven life-prolonging potential. Once it is clear that distant disease is controlled, surgery for the primary tumor can be considered, with a careful explanation to the patient that although this may aid local control, there is so far no good evidence that survival will be altered. Personally, I reserve primary tumor resection for women whose distant disease is well controlled, but the primary site is progressing despite effective systemic therapy.
Susan Pories, MD: Disagree. Patients with widespread metastatic disease at the time of presentation will not benefit from surgery and should be treated with systemic therapy. Patients with oligometastatic disease, with only one site of metastasis, can be considered for surgery if they have a good response to systemic therapy.
Statement:Regarding the timing of SLN biopsy, SLN assessment after neoadjuvant therapy is as accurate as performing the procedure prior to chemotherapy treatment.
Dr. Khan: Agree. For women who present without evidence of nodal metastases, that is, axillary nodes appear normal clinically, the effectiveness of SLN biopsy following neoadjuvant systemic therapy is well established, and is essentially equivalent to the accuracy of SLN biopsy in the primary surgical setting. The controversy at the moment relates to the use of SLN biopsy following neoadjuvant systemic therapy in women who present with involved axillary nodes. Here, the recent ACOSOG Z1071 trial suggests that use of SLN biopsy following chemotherapy is also reasonably accurate, but there are caveats and areas of concern. The overall false-negative rate in that study was just over 12%, substantially higher than what we are used to seeing in contemporary series of primary SLN biopsy. In some subsets, the false-negative rate was unacceptably high; in women who had a single SLN examined, the false-negative rate was 30%. Therefore, among women who start neoadjuvant therapy with a known positive axillary node, SLN biopsy can be offered but with readiness to change the plan to axillary dissection if only one or two SLNs are identified at surgery. Preoperative discussion with the radiation oncologist in terms of how surgical axillary management will affect the radiotherapy decisions is also helpful.
Dr. Norton: Agree, with the qualification that I interpret the term “accurate” as referring to clinical utility. Yes, neoadjuvant systemic therapy often downstages the axilla, but as we increasingly rely on tumor biology rather than anatomy for prognostication, prediction and clinical decision making, the absolute count of involved axillary lymph nodes has become less important.
Dr. Houlihan: Disagree. Studies remain controversial; however, it appears that mapping is better when the sentinel node biopsy is performed before neoadjuvant chemotherapy. False-negative rates of up to 25% have been reported after neoadjuvant chemotherapy. These results may lead to incomplete treatment in the setting of a mastectomy: no axillary dissection and possible post-mastectomy radiation therapy in certain cases.
Dr. Pories: Agree. For patients who are undergoing neoadjuvant therapy, the axilla should be assessed with ultrasound, and any suspicious lymph nodes should be biopsied with either fine needle aspiration or core biopsy under ultrasound guidance. Patients with positive biopsies will need to have full axillary dissections at the time of their definitive breast surgery. Those patients who do not have clinically positive nodes at the time of presentation and negative axillary ultrasounds can have SLN biopsy at the time of surgery.
Dr. King: Agree and disagree. The question of whether or not SLN biopsy is accurate after neoadjuvant therapy depends on the patient population in question. In the setting of clinically node-negative disease, multiple single-institution series and the NSABP B27 prospective randomized trial clearly demonstrated that SLN biopsy after neoadjuvant chemotherapy is associated with acceptable false-negative rates (less than 10% in most series) and allows node-negative patients, or those who were downstaged to node-negative status, the opportunity to avoid axillary node dissection without an increase in rates of local-regional recurrence. In the setting of clinically node-positive disease, however, the results are not as convincing. Recent data from the ACOSOG Z1071 trial, presented last December at the San Antonio Breast Cancer Symposium (abstract S2-1), demonstrated that SLN biopsy following neoadjuvant therapy in patients with a clinically positive axilla was associated with a false-negative rate of 12.6% when two or more SLNs were removed, but exceeded 20% when only one SLN was removed. These results are difficult to interpret in light of the study design, which specified a false-negative rate of 10% as a predefined study end point and are even more difficult to apply in clinical practice, given that some patients actually only have one SLN. In light of these findings, I don’t believe SLN biopsy after neoadjuvant chemotherapy in clinically node-positive patients is as accurate as SLN biopsy before chemotherapy.
Dr. Blake: Agree. The accuracy of performing SLN biopsy on a locally advanced breast cancer patient is similar whether done before or after neoadjuvant chemotherapy. The ACOSOG trial has shown an acceptable 12.6% false-negative rate in the post-neoadjuvant chemotherapy SLN biopsy patient. My practice has evolved from routinely performing SLN biopsy before neoadjuvant chemotherapy to offering it after neoadjuvant chemotherapy in a patient with a clinically negative axilla by exam, mammogram, ultrasound and breast MRI [magnetic resonance imaging] at presentation. I will, at times, proceed with a pre-neoadjuvant chemotherapy SLN biopsy in a patient with a benign fine needle aspiration in a clinically suspicious lymph node, based on my assessment of the imaging and presentation of the breast cancer.
Dr. Weiss: Disagree. The most accurate lymph node assessment is usually accomplished prior to treatment intervention.
Dr. Habibi: Agree. I have always believed that if we are doing neoadjuvant chemo and getting the benefit of the therapy to, for example, convert a mastectomy to a partial mastectomy, then why not use the same benefit when it comes to the nodal evaluation? Classic level 1 to 2 axillary dissection is associated with a significant lymphedema in around 15% of patients and with associated local numbness and paresthesia, which is bothersome to the patients. When you add the effect of radiation to this, especially now that even patients with less than three to four nodes are undergoing radiation, this can potentially impact up to 30% of patients negatively without an impact on survival. I favor doing SLN biopsy after neoadjuvant chemotherapy if the patient presents with negative axilla or if she has a complete clinical response after neoadjuvant chemotherapy.
Dr. Carlson: Disagree. Full axillary lymph node dissection is the standard therapy for node-positive breast cancer treated with neoadjuvant chemotherapy. Forty percent of patients will convert to node-negative in this setting, causing many surgeons to consider SLN biopsy to reduce potential morbidity. The literature cites a false-negative rate (FNR) for SLN biopsy in this setting of 5% to 30%, but these studies were retrospective in nature, limited by small patient numbers, and employed varying SLN biopsy techniques. At the San Antonio Breast Cancer Symposium, the results of the ACOSOG Z1071 trial found a 92.7% SLN identification and a FNR in patients with two or more SLN examined of 12.6%. The FNR was significantly lower with the use of both blue dye and radioactive colloid (10.6%) and when three or greater SLNs were examined. The conclusion of this trial was that SLN surgery was useful in node-positive patients treated with neoadjuvant therapy. Surgical technique using dual tracers and removing a minimum of two SLNs was recommended to reduce the FNR.
The SENTINA trial examined accuracy of SLN before or after neoadjuvant chemotherapy. It found that systemic treatment significantly impaired the tracer uptake and SLN detection rate. The SLN identification rate was 80.1% and FNR of SLN biopsy in patients receiving neoadjuvant chemotherapy for clinically positive axillary nodal disease was 14.2%. The study concluded that SLN biopsy was not reliable in patients who convert from node-positive to node-negative. In contrast to the ACOSOG trial, the SENTINA trial did not require biopsy confirmation of node-positive disease and didn’t use dual tracer.
Efforts to reduce the FNR after neoadjuvant chemotherapy include pre-treatment axillary ultrasound, use of dual tracers during SLN biopsy and removal of at least two SLNs. The use of post-mastectomy radiation therapy adds further controversy to this issue.
Statement:Timing of radiation with respect to breast reconstruction is controversial, given that issues such as healing and related cosmetic outcomes need to be balanced with efficacy of treatment and the potential for local recurrence. The preferred option for patients who will undergo mastectomy, desire reconstruction, and are suspected to be candidates for post-mastectomy radiation therapy is to pursue a two-stage implant-based reconstructive approach, inserting a tissue expander at the time of the mastectomy to preserve the breast envelope. Definitive reconstruction with either permanent implants or autologous tissue can then be performed once radiation has been completed.
Dr. Houlihan: Agree. We generally proceed with the second stage of reconstruction six or more months after completion of radiation therapy.
Dr. Pories: Agree. This approach preserves the skin envelope and avoids the complications of radiating a new flap or implant, which can compromise the cosmetic result.
Dr. Weiss: Disagree. The form of reconstruction that best tolerates radiation is autologous tissue. If the patient is not a candidate for this approach (too thin or contraindicated by medical/surgical problems or other risks), then reconstruction with expander, then implant, or one-step implant procedure is still possible. The risk of capsular contraction and infection is higher when radiation is given after this form of reconstruction; however, many if not most women have a very good result without significant complication. There is no “right” way: two-step or one-step done before radiation or expander, then radiation, followed by implant swap. It depends a lot on the individual patient. What does not work well is treating with excessively large expanders or implants in place that stretch the skin, flatten the chest wall, leave no valley between the breasts—because each of these factors can substantially limit the ability to optimize radiation therapy, potentially increasing complications. Plastic surgeons need to resist the temptation or the patient’s desire to make mountains out of molehills—that is, don’t make the implant-reconstructed breast larger than the original natural breast. You’re just asking for trouble if you do.
Dr. Blake: On the fence. The timing of reconstruction, whether before or after post-mastectomy radiation therapy, is not a right or wrong decision. The skill and expertise of the managing team and the needs of the patient should be determining factors on when reconstruction should be performed. Cosmetic results are subjective. It has been argued that immediate reconstruction [results] for those who require post-mastectomy radiation are inferior; however, the psychosocial impact on an individual patient not having reconstruction for almost a year after mastectomy should be considered. Certainly postoperative complications may delay therapy, but overall the delay has not been shown to alter survival rates and a significant difference in local recurrence rate has not been established. I have worked with plastic surgeons on both sides of the fence, and I feel a discussion with the patient about the pros and cons of each approach is warranted to help guide in the decision-making process.
Dr. King: Agree. As indications for post-mastectomy radiotherapy (PMRT) continue to evolve, there remains considerable controversy among radiation oncologists as to which patients will benefit from treatment. While patients with a very high chance of loco-regional recurrence (LRR) failure who clearly need PMRT are easy to identify, such as those with bulky adenopathy or inflammatory disease, there are many patients in whom the indications are much less clear and may hinge on the absolute number of involved lymph nodes or the combination of other features, such as tumor grade and lymphovascular invasion. In cases where the need for PMRT is not clear, the best option is to pursue a two-stage, implant-based reconstructive approach, inserting a tissue expander at the time of the mastectomy to preserve the breast envelope and inframammary fold. Definitive reconstruction with either permanent implants or autologous tissue, according to the patient preference, can then be performed once adjuvant systemic therapy with or without radiation has been completed. If radiation is not deemed necessary, patients can proceed with their preferred method of reconstruction following systemic therapy. If radiation is deemed necessary, patients who desire implant reconstruction can undergo the exchange procedure and proceed with PMRT to the final implant. Alternatively, patients who desire autologous tissue reconstruction can proceed with PMRT with the [tissue expander] in place, and proceed with definitive tissue reconstruction once the acute radiation skin toxicities have resolved. This approach has several advantages. first, not all patients are candidates for tissue reconstruction, so allowing them to proceed with a two-stage implant approach and irradiating the implant may be their only option for reconstruction. Second, for patients who ultimately desire tissue reconstruction, it allows them preserve the inframammary fold and undergo their definitive procedure once all treatment is complete, avoiding the potential morbidity of radiation damage to the tissue flap.
Dr. Carlson: Disagree. PMRT is increasingly used in primary treatment of breast cancer. It significantly reduces the risk of locoregional recurrence at the expense of potential cardiac and pulmonary morbidity. Meta-analysis has shown that PMRT can confer a survival benefit when used in patients with a 10% or greater risk of [locoregional recurrence]. Modern systemic therapy has significantly impacted [locoregional recurrence], further compounding the decision-making process. Preoperative workup including axillary ultrasound and possible lymph node biopsy provides valuable information for the surgical treatment planning. Radiation negatively impacts all forms of breast reconstruction. Most reconstructive surgeons feel the use of implants is contraindicated when PMRT is used and the majority will perform delayed breast reconstruction if the use of PMRT is planned prior to mastectomy. The concept of placing a temporary tissue expander under the mastectomy skin flaps has been proposed to compensate for the potential negative effects of PMRT. Some radiation oncologists feel the presence of the breast tissue expander can potentially interfere with the radiation fields and prefer the expander fluid be evacuated. This can result in seroma formation around the expander, which results in a high incidence of infection in patients receiving radiation. Even if the expander is not deflated, the risk of expander loss is increased because of radiation. If successful, the radiated skin flaps frequently become fibrotic, which, if not resected at the time of reconstruction, can have a negative impact on the aesthetic outcome.
Dr. Habibi: Agree. This has several advantages. first, the radiation can be administered sooner; it is easier to coordinate the timing of surgery between surgical oncologist and the plastic surgeon to do a tissue expander than the full reconstruction. Second, the effect of radiation on reconstructed breast can be significant, especially autologous flaps like deep inferior epigastric perforator (DIEP) flaps. In our practice, we preferentially offer autologous flaps to patients with radiation. We feel that exchanging the tissue expander and bringing new healthy tissue with blood supply to the radiated field will be beneficial to the final cosmetic outcome.
Dr. Khan: Agree. For women who need mastectomy and desire reconstruction, placement of a tissue expander at the time of mastectomy does preserve more skin and lead to somewhat better reconstruction outcomes, although this is a matter of degree, and certainly deferred reconstruction can also provide good results. However, immediate expander reconstruction is associated with higher complication rates (hematoma, flap necrosis, infection and return to the operating room), and this fact should be discussed with patients whose tumors display adverse features that suggest a possibility of PMRT. Issues of radiation planning, particularly on the left side and particularly in older women or those at risk for cardiac disease, should also be discussed, and again a preoperative consultation with a radiation oncologist may be helpful. For most women, immediate expander reconstruction can be safely pursued, but an airing of all these issues is necessary. Another option to consider if the PMRT decision will be mainly driven by nodal findings is initial SLN biopsy as a separate procedure prior to mastectomy. Once the nodal status is confirmed, the radiotherapy plan can be clarified, and reconstruction planning can proceed accordingly.
Statement:It is appropriate for a gene, such as BRCA1/BRCA2, to be patented by the individual or company that discovered the gene, such as Mark Skolnick/Myriad Genetics in the case of BRCA1 and BRCA2, and for those individuals or companies to therefore possess the exclusive right to perform clinical tests or research on said gene(s).
Dr. Houlihan: Disagree. Although patents reward the inventors for their discovery, a patent prevents other researchers from developing diagnostic tests and possible treatment interventions, which may slow down progress in those areas. It also makes a test more expensive because there is a monopoly. There are also many ethical issues regarding a patent on a part of nature and life, which is a moral issue yet to be sorted out by the inventors, patients and their families.
Dr. Blake: On the fence. I would interpret a gene to be a naturally occurring entity that should not have been considered for patent to begin with, but BRCA1/BRCA2 and thousands of other genes have already been patented. If the Supreme Court does reverse Myriad’s patent on the gene BRCA1/BRCA2, the concern surrounding the future of research in genetics is warranted. The impact of having an incentive to do research cannot be denied and would no longer be present if the ability to patent a gene is lost. If Myriad and other companies are allowed to maintain their patent of a gene, the system utilized in other countries that offers an exception to allow for ongoing research of a gene while under patent would help to stimulate research. I feel less strongly about companies having a patent that allows them to perform clinical testing on a gene if they have researched and developed the test.
Dr. Weiss: Disagree. While we certainly need incentives for companies to heavily invest in research on genetic and protein sequencing, it’s unacceptable for a patent to interfere with scientific progress that depends on access to the discovery. Impeding such critical progress is a bad outcome.
Dr. Habibi: On the fence. Let’s not forget that the discovery of these genes was made possible by grants from the federal government and taxpayers. I do not discount the genius of the researchers and the fact that they ought to be compensated. After several years, however, other labs should be able to offer the service. The Myriads still will have the majority of market share, but the price for the health system should not be this high.
Dr. Carlson: Disagree. Currently more than 20% of the human genome has been patented. These patent rights include the gene sequences themselves and any resulting applications developed from them, including laboratory tests and targeted drug therapies. This month [June], the Supreme Court will hear the case against the patent protection of Myriad Genetics of the BRCA1/BRAC2 genes. [On June 13, the U.S. Supreme Court unanimously ruled that natural human genetic sequences cannot be patented.] Patents such as these have the potential to slow further innovations by blocking the research and development efforts of outside parties using the basic constructs patented by other companies.
Dr. Khan: Disagree. The patenting of genes is patently absurd. It deprives society of the benefits of scientific progress, contributes to social injustice, and retards scientific progress in the field. Although it is reasonable for companies to profit from their investment in technology, exclusive patents lasting for decades are manifestly unjust. We need to find other ways to allow reasonable compensation without strangling development of far cheaper and widely available genetic testing that would have been available by now were it not for existing patents.
Statement:Provided that certain oncologic and practical criteria are applied, nipple-sparing mastectomy provides the benefits of less invasive surgery and improved cosmetic outcomes without increased oncologic risk in appropriately selected patients.
Dr. Pories: Disagree. This makes it impossible to move the field forward. While I can see patenting a test, it makes no sense to patent a gene.
Dr. Weiss: Generally agree. Current data show that cancer of the nipple ducts is exceedingly rare, and sparing the areola involves the same risk as regular skin sparing. If the cancer is close to the nipple, sparing the nipple is not worth the risk of leaving it intact.
Dr. Houlihan: Agree. In women with cancers or ductal carcinoma in situ (or DCIS) more than 2.5 cm from the nipple, nipple-sparing mastectomy is a reasonable option. The procedure is more difficult in the setting of a very large breast or if there is significant ptosis. Women also must be informed of the fact that the nipple will be insensate.
Dr. Norton: On the fence. It depends heavily on the clinical presentation and the skill of the surgeon.
Dr. Carlson: Agree. The aesthetic results of nipple reconstruction after skin-sparing mastectomy and reconstruction can be disappointing. Data has shown that the patient satisfaction with nipple preservation is much higher than if a nipple is reconstructed. An increasing body of literature has shown a low incidence of nipple [cancer] recurrence after nipple-sparing mastectomy in the treatment of selected patients with early breast cancer. Despite this, long-term follow-up data is lacking. Sakurai et al recently published their experience with 788 therapeutic nipple-sparing mastectomies, which were compared with a cohort of 144 patients who were treated with conventional mastectomies (Med Oncol 2013;30:481). The two groups were similar in disease stage and tumor size. None received radiation. In the nipple-sparing mastectomy group, nipple-areola complex recurrence was observed in 3.7%. At five and 10 years, disease-free survival was 86% and 83%, compared with 83% and 80% in the mastectomy group. The median follow-up for this study was 78 months.
Dr. Khan: Agree. Nipple-sparing mastectomy leads to improved cosmetic outcomes in appropriately selected patients, and there are emerging data that locoregional outcomes are no different in women receiving this procedure compared with conventional mastectomy. The surgical series that have been reported are now of good size, ranging from several hundred patients upward, and although favorable long-term data have been reported from some groups, the overall follow-up period in a recent systematic review was only in the two- to three-year range. The conservative approach would therefore be to offer it only to women undergoing mastectomy for prevention, and those with early, favorable tumors where recurrence risk can be expected to be low. Other caveats are that it must be a complete mastectomy with no compromise in the extent of resection of breast tissue compared with conventional mastectomy procedures, and that tumor must not be located in the vicinity of the nipple, although the closest tolerable distance between tumor and nipple is not generally agreed upon. The benefit of base-of-the-nipple biopsy and frozen section during surgery is questionable since it can be associated with both false-positive and false-negative findings. Inframammary fold incisions provide the best cosmesis and do not compromise nipple or flap viability, and therefore are my preferred approach.
Dr. Pories: Agree. Nipple-sparing mastectomies are appropriate for patients undergoing prophylactic surgery and can also be offered to breast cancer patients who have tumors that are at least 2 cm away from the nipple. However, the terminology “less invasive” is misleading, and patients must be aware that there is a chance that the nipple may have to be removed at a second procedure after the mastectomy if the blood supply is poor and there is necrosis of the nipple or if cancer is found in the nipple plug, which should be sent as a separate specimen.
Dr. Habibi: Agree. Nipple-sparing mastectomy has changed the landscape of breast surgery in the last decade. One can make an argument that the breast is defined by the nipple-areola complex. With emphasis on oncologic and practical criteria, nipple-sparing mastectomy can improve the cosmetic outcome tremendously. I would not consider it a less invasive operation, as it is much more complex and difficult than regular skin-sparing mastectomy. The thickness of the flaps, nipple-areola complex and the completeness of mastectomy is more complicated in nipple-sparing mastectomy; having said that, in the right hands the results can be oncologically safe and cosmetically outstanding.
Dr. Blake: Agree. A nipple-sparing mastectomy can have great cosmetic results without increasing oncologic risk; however, I question describing it as a less invasive surgery. The incision for a nipple-sparing mastectomy is frequently on par with that of a skin-sparing simple mastectomy. I am comfortable with recommending this procedure for risk reduction, but I am very selective in offering a nipple-sparing mastectomy for a patient with breast cancer. Publications on the oncologic safety of nipple-sparing mastectomy have made me more comfortable with offering this to patients with breast cancer than I was a few years ago. I am optimistic that the American Society of Breast Surgeons Nipple Sparing Mastectomy Registry will provide helpful information on this procedure’s utilization and cosmetic and oncologic outcomes.