Back to the Future: Why Are More Women Having Bilateral Mastectomy for Unilateral Breast Cancer?

In 2002, reports by Fisher¹ and Veronesi² affirmed the long-term validity of breast-conserving surgery (BCS) for the management of early-stage breast cancer (ESBC). BCS is defined as lumpectomy with postoperative whole breast irradiation. Years earlier, in 1991, a National Cancer Institute Consensus Conference endorsed BCS over mastectomy as the preferred treatment of ESBC. Over the years, this led to a decrease in mastectomy rates. By 2003, BCS rates in the United States were approaching 69%.³ Surprisingly, this upward trend reversed after 2003, with the rate of women treated with BCS declining to 58%.⁴ The decrease in BCS has undermined the progress made over the last three decades in the management of ESBC, which has been firmly based on an accumulation of biological and clinical evidence of the natural history of this disease.

It is difficult to fathom why rates of BCS are declining at a time when the average size of breast tumors in the United States is <2 cm at diagnosis. With increasingly smaller tumors, one might wonder why rates of margin positivity following BCS are as high as 31% to 50%.^5,6 Nearly 50% of women who elect BCS must undergo subsequent mastectomy to clear these positive margins.⁷ Once informed consent has been obtained, the success of BCS is completely in the hands of the surgeon at the time of lumpectomy. This problem is not new, of course, and there are other factors that have contributed to the recidivism to mastectomy.

The Problem With the Ipsilateral Breast

The recent discovery of the potential for magnetic resonance imaging (MRI) to reveal second cancers in a breast affected by ESBC has led many clinicians to recommend and patients to choose mastectomy for this ipsilateral breast. MRI of the ipsilateral breast reveals potential second tumors in as many as 13% to 30% of patients.^8,9 The fact that second lesions are often found in a breast with ESBC is actually a “rediscovery,” because Holland described this likelihood more than 20 years ago, after performing detailed serial section histologic examinations of mastectomy specimens. Holland’s data suggested that as many as two-thirds of these patients had a second lesion within the same breast, most of which were located within 4 cm of the known primary.¹⁰ Holland’s data remains timely because, at the time, it was used as an admonition about the validity of BCS. The rediscovery with MRI that many patients have second lesions in the ipsilateral breast is being revisited as a reason for the increasing conversion from BCS to mastectomy in patients with ESBC.^11,12

Paradoxically, Japanese investigators recently offered an analysis similar to Holland’s to support the use of accelerated partial breast irradiation (APBI), which spares breast tissue outside of this 4-cm radius from radiation in women who undergo BCS.¹³ Favorable 4-year recurrence rates of 1% have been published for APBI; patients continue to be followed, and longer outcomes associated with APBI are expected in the future.¹⁴ Not surprisingly, a recent report shows that patients selected for BCS on the basis of unifocal disease identified by MRI and similarly treated patients who undergo BCS based on unifocal disease established by routine mammography have identical local recurrence rates (3%-4%) at 8 years’ follow-up.¹⁵

This compares favorably to the recent update by the Early Breast Cancer Trialists’ report, which shows 10-year local failure rates of 8% for node-negative women undergoing mastectomy and 27% for node-positive women similarly treated. The addition of radiotherapy even in mastectomy patients led to a salutary decrease in local failure rates.¹⁶ In women undergoing systemic hormonal ablation or chemotherapy, local failure rates of 7% were noted by the National Surgical Adjuvant Breast and Bowel Project in a review of several of their trials involving BCS.¹⁷

With increasingly smaller cancers disclosed by effective mammographic screening, the weight of 25 years of clinical experience, and the improvement in systemic therapies to date, it is difficult to see how the rediscovery of the long-recognized existence of subclinical tumors, which are mostly noninvasive and well controlled by contemporary radiotherapy, should discourage physicians and patients alike from BCS. As shown by the Mayo Clinic report, preoperative MRI raised a woman’s odds of undergoing mastectomy by 60% in 2006. Just having surgery in 2006 vs having surgery in 2003 raised her odds of having a mastectomy by 70%.³ This decrease in BCS is attributed to the use of MRI in 2006. Bleicher just reported similar increases in mastectomy rates in patients undergoing preoperative MRI (19% vs 27%).¹⁸

The Problem With the Contralateral Breast

The introduction of MRI in breast diagnostics, coupled with inadequate risk assessment by clinicians and understandably fearful patients, has led to unnecessary preventive contralateral prophylactic mastectomy (CPM) in patients with ESBC. Many breast cancer specialists see second opinion requests for patients, young and old, who have opted for contralateral prophylactic mastectomy based on an MRI finding, without any histologic proof of cancer. Invariably, many clinicians making this recommendation do not have the ability to perform MRI-guided core biopsy of lesions not visible with mammography or ultrasonography. The distressing report by Tuttle has shown an increase in contralateral mastectomy from 4.2% in 1998 to 11% in 2003.⁴ In this report of 152,755 patients included in the Surveillance, Epidemiology and End Results cancer registry, 8.3% were aged ≥60 years at the time of contralateral mastectomy. Understandably, this figure increased to 25% among women aged 18 to 49 undergoing unilateral mastectomy for the treatment of their breast cancer. There can be no question that the greater use of MRI has accelerated this trend, as Tuttle’s report also shows that the contralateral mastectomy rate increased between 2000 and 2003.⁴

It is concerning that the most common reason for CPM was physician’s advice regarding the risk of contralateral breast cancer. This negligible risk has been documented since the days of radical mastectomy and demonstrates how inadequate informed consent can be. The risk of contralateral disease is well established as 3% at 5 years.¹⁹ Furthermore, any risk of contralateral disease declines by 50% for patients using tamoxifen and 20% for those treated with chemotherapy.¹⁶ Clearly, prophylactic removal of the unaffected breast can have no impact on the survival of a patient in whom the stage of her index cancer is the primary determinant of survival.

Remarkably, even in high-risk breast cancer patients undergoing prophylactic mastectomy, MRI missed 3 of 4 lesions noted at final pathology (of these, three-quarters were ductal carcinoma in situ), yet added great expense.²⁰ At present, there is no question that the growing use of MRI by physicians unfamiliar with all its limitations, coupled with patients’ fear and an inadequate risk assessment, lead to the difficult conversations surgical oncologists have with patients at the time of informed consent. Many surgical oncologists find all the information hard to convey in a single visit. A thorough discussion may need to encompass information on pursuing reliable alternative surveillance and prevention strategies, along with accurate genetic risk assessment and its limitations, before resorting to alternatives that pre-date the Fisher-Veronese era of progress in breast cancer management.²¹ It is this wonderful explosion in our knowledge about breast cancer more than anything that affirms the need to use evidence-based algorithms within specialized multidisciplinary breast centers to care for the complicated problem of breast cancer.

References

1. 1. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233-1241.
2. 2. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347(16):1227-1232.
3. 3. Katipamula R, Degnim AC, Hoskin T, et al. Trends in mastectomy rates at the Mayo Clinic Rochester: effect of surgical year and preoperative magnetic resonance imaging. J Clin Oncol. 2009;27(25):4082-4088.
4. 4. Tuttle TM, Habermann EB, Grund EH, Morris TJ, Virnig BA. Increasing use of contralateral prophylactic mastectomy for breast cancer patients: a trend toward more aggressive surgical treatment. J Clin Oncol. 2007;25(33):5203-5209.
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7. 7. Cellini C, Huston TL, Martins D, et al. Multiple re-excisions versus mastectomy in patients with persistent residual disease following breast conservation surgery. Am J Surg. 2005;189(6):662-666.
8. 8. Bluemke DA, Gatsonis CA, Chen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JAMA. 2004;292(22):2735-2742.
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10. 10. Holland R, Veling SH, Mravunac M, Hendriks JH. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 1985;56(5):979-990.
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16. 16. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087-2106.
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18. 18. Bleicher RJ, Ciocca RM, Egleston BL, et al. The influence of routine pretreatment MRI on time to treatment, mastectomy rate, and positive margins. In: Proceedings from the American Society of Clinical Oncology Breast Cancer Symposium; 2008; Washington, DC. Abstract 227.
19. 19. Gao X, Fisher SG, Emami B. Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2003;56(4):1038-1045.
20. 20. Black D, Specht M, Lee JM, et al. Detecting occult malignancy in prophylactic mastectomy: preoperative MRI versus sentinel lymph node biopsy. Ann Surg Oncol. 2007;14(9):2477-2484.
21. 21. Schwartz MD. Contralateral prophylactic mastectomy: efficacy, satisfaction, and regret. J Clin Oncol. 2005;23(31):7777-7779.

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Edibaldo Silva, MD, PhD, is an associate professor of surgical oncology, Division of Surgical Oncology, at the University of Nebraska Medical Center in Omaha and a member of the editorial advisory board for Oncology & Biotech News and Oncology Net Guide.