Facts, not fear, should guide decisions about contralateral prophylactic mastectomy

The percentage of women with invasive breast cancer who undergo contralateral prophylactic mastectomy has skyrocketed, even though evidence suggests the procedure confers no survival benefit for average-risk women.

The American Society of Breast Surgeons has undertaken an extensive awareness effort to reverse this trend, which its members say is driven too often by fear rather than science.

In June, the society cautioned against routine use of double mastectomy as part of the American Board of Internal Medicine Foundation’s Choosing Wisely campaign, designed to identify common tests and procedures that are not always necessary.

The society suggested double mastectomy should not be performed in patients who have a single breast with cancer until they are informed there generally is a low risk that they will develop cancer in the other breast, and that the effect of the procedure on life expectancy is minimal.

The society went a step further in July, issuing a position statement that recommended against contralateral prophylactic mastectomy (CPM) for average-risk women with unilateral breast cancer.

The statement — which summarizes key data and offers guidelines about appropriateness of prophylactic surgery — provides a framework for clinician–patient discussion, according to Judy C. Boughey, MD, FACS, professor of surgery at Mayo Clinic in Rochester, Minnesota, and the statement’s lead author.

Photo courtesy of Mayo Clinic.

“The lack of a clear survival advantage from CPM has been part of the routine discussion with patients considering CPM for many years,” Boughey told HemOnc Today. “Our hope is that this position statement helps physicians counsel patients considering CPM, and ensures that patients are well informed about the advantages and disadvantages of the procedure. Patients should know the facts, and this will allow for informed, shared decision-making.”

HemOnc Today spoke with breast surgeons and oncologists about the factors that have contributed to the dramatic increase in CPM; the controversy over its use in average-risk patients; and the need for clinicians, surgeons and patients to be well informed about the benefits and risks.

A ‘sustained, sharp rise’

Mehra Golshan, MD, distinguished chair in surgical oncology at Brigham and Women’s Hospital and medical director of International Oncology Programs at Dana-Farber/Brigham and Women’s Cancer Center, and colleagues used SEER data to assess trends in CPM use among 496,488 women diagnosed with unilateral stage I to stage III breast cancer between 1998 and 2012.

The results — published in April in Annals of Surgery — showed considerably more women underwent breast-conserving surgery (59.6%) or unilateral mastectomy (33.4%) than CPM (7%).

However, the proportion of women who underwent CPM tripled over time, from 3.9% in 2002 to 12.7% in 2012 (P < .001). Rates of unilateral mastectomy declined during the study period, from 36.7% to 28.4%, whereas rates of breast-conserving surgery remained stable.

Women who underwent mastectomy plus CPM were more likely than those who underwent breast-conserving surgery or unilateral mastectomy to be younger (median age, 50 years vs. 60 years vs. 59 years), be non-Hispanic white (80.4% vs. 69.1% vs. 75%) and have invasive lobular histology (12.7% vs. 7.1% vs. 10.6%).

Use of reconstructive surgery was more common among women who underwent CPM than breast-conserving surgery (48.3% vs. 16%).

Despite increased utilization of CPM, analyses adjusted for age and other disease factors showed the procedure did not improve breast cancer–specific survival (HR = 1.08; 95% CI, 1.01-1.16) or OS (HR = 1.08; 95% CI, 1.03-1.14) compared with breast-conserving surgery.

“Our analysis highlights the sustained, sharp rise in popularity of CPM, while contributing to the mounting evidence that this more extensive surgery offers no significant survival benefit to women with a first diagnosis of breast cancer,” Golshan said in a press release.

The “mounting evidence” Golshan described includes a paper by Lostumbo and colleagues published in 2010 in Cochrane Database of Systematic Reviews.

Their analysis of 39 observational studies revealed CPM was associated with reduced incidence of contralateral breast cancer, but improvements in disease-specific survival were inconsistent.

In one of the studies analyzed, researchers tried to control for several differences between intervention groups. However, results showed no OS advantage for CPM at 15 years.

Another study showed an association between CPM and longer survival but, after adjustments for receipt of bilateral prophylactic oophorectomy, the effect of CPM on all-cause mortality was no longer significant.

“When a patient does develop a cancer in the opposite breast, it is usually at an early stage, as the patient is being screened regularly,” Todd M. Tuttle, MD, MS, surgical oncologist at University of Minnesota, told HemOnc Today. “If you combine the fact that you have a low risk for developing a cancer with the low risk you have for dying of that other cancer, we really knew quite a long time ago that there is no survival benefit from having your opposite breast removed.”

The fear factor

Evidence suggests patient fear is the primary driver of CPM utilization.

A study by Jagsi and colleagues, published last year in Journal of Clinical Oncology, showed 92% of patients who underwent CPM factored “peace of mind” into their decision.

In another study, Hawley and colleagues used the Detroit and Los Angeles SEER registries to conduct a longitudinal survey of women newly diagnosed with breast cancer.

The analysis — results of which were published in 2014 in JAMA Surgery — included 1,447 women; of this group, 18.9% strongly considered CPM and 7.6% underwent the procedure.

The majority (78.1%) of those who underwent CPM indicated worry about recurrence affected their decision.

Women with greater worry about recurrence were significantly more likely to undergo CPM than breast-conserving surgery (relative risk ratio [RRR] = 4.24; 95% CI, 1.8-9.98) or unilateral mastectomy (RRR = 2.81; 95% CI, 1.14-6.88).

However, this decision is not grounded in science, experts contend.

The American Society of Breast Surgeons position statement notes that CPM does not improve the cure rate of the initial cancer, nor reduce its risk for recurrence.

“We typically consider recurrence of breast cancer to signify metastasis or local recurrence of the original cancer,” Debu Tripathy, MD, professor in and chair of the department of breast medical oncology at The University of Texas MD Anderson Cancer Center and a HemOnc Today Editorial Board member, told HemOnc Today. “This is very important to distinguish from a new primary breast cancer, because a metastasis is not curable. Some patients would confuse a metastatic spread of the first cancer with a new cancer in the other breast — which, of course, does not have anywhere near the same implications. Most contralateral breast cancers have a very high cure rate.”

In the study by Hawley and colleagues, most women (68.9%) in the cohort who underwent CPM did not have major genetic or familial risk factors that increased their likelihood for contralateral disease.

However, these women have a relatively low risk for cancer in their unaffected breast, experts contend.

The American Society of Breast Surgeons paper, which summarizes the available data, estimated average-risk women diagnosed with cancer in one breast have a 2% to 6% chance for developing cancer in the opposite breast over the subsequent decade.

“Despite the availability of tamoxifen and aromatase inhibitors indicated for ER–positive cancers that are known to reduce the contralateral breast cancer risk by more than 50%, some women overestimate the risk for contralateral breast cancer and opt for CPM,” Charles L. Shapiro, MD, co-director of the Dubin Breast Center at Mount Sinai Hospital and a HemOnc Today Editorial Board member, said in an interview.

Even when women understand CPM likely will not extend their survival, they still may derive considerable psychosocial reassurance from the procedure, according to results of a study by Rosenberg and colleagues.

In that study — published in 2013 in Annals of Internal Medicine — 94% of women indicated their desire to improve survival was either extremely important or very important in their decision to undergo CPM. However, only 18% indicated they believed women who underwent CPM would live longer than those who did not.

“These apparently contradictory findings highlight the heightened sense of anxiety that women feel when they are making these decisions and emphasize the need for clear communication and shared decision-making between patients and their physicians,” Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS(C), director of The Breast Center at Smilow Cancer Hospital at Yale-New Haven and assistant director of global oncology at Yale Comprehensive Cancer Center, wrote in a review published this year in American Journal of Hematology/Oncology.

Patient-reported outcomes

Even with a lack of survival benefit, patients may opt to undergo CPM for perceived quality-of-life benefits.

“Some women simply do not want to deal with the prospect of having continued mammograms, or the possibility that a mammogram in the future will indicate a biopsy,” Shapiro said. “They will perceive their quality of life better if they do not have to have subsequent breast cancer screening or imaging, breast biopsies, or the worry and anxiety that goes along with that.”

However, Hwang and colleagues — who conducted a national cross-sectional survey to assess patient-reported outcomes among women with a history of breast cancer surgery — suggested the quality-of-life benefits may be minimal.

The researchers administered electronic surveys to evaluate the association between CPM and four domains within BREAST-Q, a validated breast surgery outcomes patient-reporting tool.

The analysis — published this year in Journal of Clinical Oncology — included 3,977 women who underwent mastectomy and 1,598 who underwent CPM.

Among women who did not undergo breast reconstruction, CPM conferred no significant benefit in any quality-of-life domain. Among women who underwent breast reconstruction, those who chose CPM reported higher breast satisfaction scores (62 vs. 59.9; P = .0043) but lower physical well-being (74.5 vs. 76.8; P < .001) and lower psychosocial well-being (71.7 vs. 73.9; P = .0051).

Multivariable analysis showed psychosocial well-being (beta = 1.8) and breast satisfaction (beta = 1.49) were significantly higher among women who underwent CPM; however, receipt of breast reconstruction had considerably greater impact than CPM on psychosocial well-being (beta = 4.56), breast satisfaction (beta = 5.58) and sexual well-being (beta = 6.83).

“As more patient-reported quality-of-life data become available, such information will be increasingly essential to share and review with patients when counseling women contemplating CPM as part of their breast cancer treatment,” Hwang and colleagues wrote.

Still, cosmesis is a key consideration, and advances in breast reconstruction have made CPM a more cosmetically appealing option than unilateral mastectomy.

In her review, Chagpar cited a study by Koslow and colleagues, published in 2013 in Annals of Surgical Oncology, that showed women who underwent CPM were significantly more likely than those who underwent unilateral reconstruction to report satisfaction with their breasts as measured by BREAST-Q patient-reported outcomes instrument (64.4% vs. 54.9%; P < .001).

“Studies have found a direct correlation between reconstruction and the decision to have CPM, and more than 40% of patients who opt for CPM cite cosmesis as one of their motivating factors,” Chagpar wrote. “Indeed, most patients — 83% to 97% — who choose this procedure state they are highly satisfied with their decision, and 84% to 96% would make the same decision again.”

Surgeon’s knowledge

The American Society of Breast Surgeons’ position statement urges physicians to counsel patients about the advantages and disadvantages of CPM, allowing for informed decision-making.

However, in a study published last year in JAMA Surgery, Yao and colleagues concluded a considerable portion of surgeons lack sufficient knowledge about CPM and may need additional training before they can effectively counsel patients about the procedure.

The researchers emailed surveys to 2,436 active members of the society. The surveys presented two clinical cases and three factual questions developed by breast surgeons and medical oncologists.

Of the 592 survey respondents, 232 (39.2%) had a low level of knowledge.

“This is an alarming figure among supposed experts in breast cancer,” Tuttle told HemOnc Today.

Surgeons scored 85% or better on questions related to the survival benefit conferred by CPM, as well as the 5- to 10-year risks of contralateral breast cancer among patients who had no additional risk factors. However, they exhibited less knowledge about contralateral breast cancer risk for specific subgroups, such as patients who harbored BRCA mutations and those who had lobular carcinoma.

“What is not clear is how surgeons’ knowledge translates into treatment patterns,” Yao and colleagues wrote. “Are patients undergoing CPM more frequently because surgeons are not adequately informing them? Could this be because the surgeons themselves are not well informed?”

The findings highlight the need for decision aids or teaching materials that can inform patients with newly diagnosed breast cancer about the potential utility of CPM, Yao and colleagues wrote.

“Patients should understand the lack of survival benefit and potential risks and complications of CPM to help them make an informed decision that is in keeping with their personal values,” Boughey said.

This counseling must encompass several components, Tuttle said.

“It is important to try to provide patients with the best estimate of what their risk for developing a cancer in their opposite breast is — for average-risk patients, this is low,” Tuttle said. “It is also important to talk about some of the side effects of removing the healthy breast, such as increased hospital stay, increased surgical complications and use of drains. The physician or surgeon also should talk about the optimal strategies if not removing the opposite breast, such as examinations and the types of imaging that can be performed.”

Chagpar expressed hope that those conversations are happening.

“I would hope that surgeons are always performing CPM in the context of a detailed and informed discussion of the risks and benefits tailored to the patient’s individual risk,” Chagpar told HemOnc Today. “Perhaps the problem is that surgeons know too much data. There are data to support multiple claims on both sides of the CPM debate.

“Ultimately, though, there is no absolute answer that applies to all patients,” Chagpar added. “For example, this procedure is likely not going to benefit an 80-year-old patient with a tiny tumor, but the same may not hold for a 20-year-old who may benefit from symmetry, peace of mind and reduced imaging, on top of real benefits in terms of risk reduction.”

Although surgeons may understand the relative risk reduction conferred by CPM and the absolute risk for developing contralateral breast cancer, the risk for a specific individual is less clear.

“Absolute risk for cancer development is not well known for any individual patient for any cancer type,” Boughey said. “Even for women with BRCA mutations, the exact risk for breast cancer development is not known, just as we cannot accurately predict who will have a heart attack or who will develop diabetes, and when.”

Potential complications

The potential for infection or other chronic problems after CPM also must be factored into a patient’s decision.

Miller and colleagues conducted a single-institution study of 600 patients newly diagnosed with unilateral breast cancer to determine whether those who underwent CPM experienced more complications than those who underwent unilateral mastectomy.

Researchers assessed minor complications — which included minor bleeding, aspirations, infections that required antibiotics, delayed wound healing, and partial flap or nipple necrosis — and major complications, which included seroma or hematoma that required operation, infection that required rehospitalization, implant removal, or flap or nipple loss.

Sixty-five percent of the cohort underwent unilateral mastectomy and one-third (35%) underwent CPM.

The results — published in 2013 in Annals of Surgical Oncology — showed patients who underwent CPM were more likely to experience any complication (41.6% vs. 28.6%; P = .001) or a major complication (13.9% vs. 4.1%; P < .001).

After adjustments for age, BMI, diabetes and smoking history and other factors, patients who underwent CPM were significantly more likely than those who underwent unilateral mastectomy to experience any complication (OR = 1.53; 95% CI, 1.04-2.25) or a major complication (OR = 2.66; 95% CI, 1.37-5.19).

“I provide my patients with all the evidence that I can give them,” Tripathy said. “I counsel them and my advice, most often, is not to do it, as breast surgery has a risk for infection and chronic problems. They are not common, but they do happen. This has to be taken into account.”

Appropriate use and the value question

The American Society of Breast Surgeons’ position statement concluded CPM should be considered for women at significant risk for contralateral breast cancer. This group includes women with BRCA mutations, a strong family history of the disease, or a history of mantle chest radiation prior to age 30 years.

The procedure also may be considered for those with other genetic risks, or for women who do not have genetic risks but do have strong family histories of breast cancer.

In addition, the statement labeled CPM as potentially appropriate in other cases, such as to limit contralateral breast surveillance, improve reconstructed breast symmetry, manage risk aversion or manage extreme anxiety.

The society discouraged CPM for women at average risk with unilateral breast cancer or advanced index cancer, those at high risk for surgical complications, and BRCA–negative women who have a family member who carries a BRCA mutation.

The society also recommended clinicians discuss several facts with patients, including that CPM:

• does not protect 100% against contralateral breast cancer;

• will not improve the cure rate for or recurrence risk of the initial cancer;

• will not reduce the need for additional treatments for the initial cancer; and

• results in permanent numbness of the chest wall and nipple, if preserved.

Although physician education is essential, a broad effort is necessary to disseminate this information to patients because they ultimately drive the decision, Tripathy said.

“One of the biggest motivating factors for patients with cancer is fear — fear of recurrence or not wanting to have to undergo postoperative surveillance,” he said. “All of this information has to be discussed and included in these materials.”

The society’s position statement is intended to foster discussion that “does not set a mandate against CPM in cases for which it may be very appropriate,” Chagpar said.

Clinicians also should be encouraged — and feel empowered — to present this information to patients, she said.

“When I think a patient is making a decision that I’m not sure she understands, or if I believe she is making her decision based upon fear rather than knowledge, it is important for me to gauge her knowledge and understand her rationale,” Chagpar said. “If the patient says it is because she wants to live to see her grandkids, I tell her that this procedure will not influence her longevity. Hopefully she will live to see her grandkids with or without CPM.

“If — after an informed discussion — she tells me that she understands her risk, but because she is young with a long life expectancy and a strong family history of breast cancer, she wants to minimize her risk while achieving symmetry and reducing the need for imaging, understanding that there may be no improvement in survival, and increased operative time and potential complications, then CPM is reasonable,” she added.

If — after informed counsel — a patient still feels strongly about undergoing CPM, Tripathy said he does not stand in her way.

“I let the patient discuss it with their surgeon,” he said. “If one could undergo surgery with no complications, maybe it would be a reasonable thing to do. But the small benefits have to be balanced against the risks for additional surgeries — and the costs, as well.”

In the rapidly changing health care landscape, cost soon may play a greater role in the CPM debate, Shapiro said.

“We are still in a fee-for-service world, and we are just beginning to transition to a value-of-care world in which bundled payments for episodes of total care,” Shapiro said. “Value of care will become increasingly important in terms of what drives health care expenditures. It may very well influence decisions like whether someone undergoes CPM.” – by Jennifer Southall

References:

Boughey JC, et al. Ann Surg Oncol. 2016;doi:10.1245/s10434-016-5408-8.

Boughey JC, et al. Ann Surg Oncol. 2016;doi:10.1245/s10434-016-5443-5.

Chagpar AB. Contralateral prophylactic mastectomy: Pros and cons. 2016. Available at: www.gotoper.com/publications/ajho/2016/2016apr/contralateral-prophylactic-mastectomy-pros-and-cons. Accessed on Sept. 26, 2016.

Evans DG, et al. Breast Cancer Res. 2015;doi:10.1186/s13058-015-0650-8.

Hawley ST, et al. JAMA Surg. 2014;doi:10.1001/jamasurg.2013.5689.

Hwang, ES, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2015.61.5427.

Jagsi R, et al. Abstract #1011. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Koslow S, et al. Ann Surg Oncol. 2013;doi:10.1245/s10434-013-3026-2.

Lebo PB, et al. Cancer. 2015;doi:10.1002/cncr.29461.

Lostumbo L, et al. Cochrane Database Syst Rev. 2010;doi:10.1002/14651858.CD002748.pub3.

Miller ME, et al. Ann Surg Oncol. 2013;doi:10.1245/s10434-013-3108-1.

Raphael J. Abstract #44. Presented at: Breast Cancer Symposium; Sept. 4-6, 2014; San Francisco.

Rosenberg SM, et al. Ann Intern Med. 2013;doi:10.7326/0003-4819-159—6-201309170-00003.

Wong SM, et al. Ann Surg. 2016;doi:10.1097/SLA.0000000000001698.

Yao K, et al. JAMA Surg. 2015;doi:10.1001/jamasurg.2015.3601.

For more information:

Judy C. Boughey, MD, FACS, can be reached at Mayo Clinic, 200 First St. SW, Rochester, MN 55905; email: boughey.judy@mayo.edu.

Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS (C), can be reached at The Breast Center-Smilow Cancer Hospital at Yale-New Haven, 20 York St., New Haven, CT 06510; email: chagpar@yale.edu.

Charles L. Shapiro, MD, can be reached at Tisch Cancer Institute, 1 Gustave L. Levy Place, Box 1079, Annenberg Building, Room A24-64, New York, NY 10029; email: charles.shapiro@mssm.edu.

Debu Tripathy, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1354, Houston, Texas 77030; email: dtripathy@mdanderson.org.

Todd M. Tuttle, MD, MS, can be reached at The University of Minnesota, 420 Delaware St. SE, Mayo Mail Code 195, Minneapolis, MN 55455; email: tuttl006@umn.edu.

Disclosure: Boughey, Chagpar, Tripathy, Tuttle and Shapiro report no relevant financial disclosures.

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