The powerful and important study by Kurian et al,1 reviewed in this issue of The ASCO Post, adds vital information to the discussion regarding use of contralateral prophylactic mastectomy among patients with unilateral breast cancer in the United States.2,3 Based upon data from the California Cancer Registry, this study looked at surgical treatment patterns as well as outcomes for nearly 200,000 breast cancer patients diagnosed between 1998 and 2011. As has been shown by others,4-6 bilateral mastectomy rates have increased over time, and contralateral prophylactic mastectomy tends to be more common among white American and socioeconomically advantaged patients.
A relatively novel and extremely compelling aspect of the Kurian et al study is the inclusion of outcomes data for breast-conserving surgery patients, as most prior studies have compared outcomes for unilateral vs bilateral mastectomy among patients with unilateral disease. Kurian et al demonstrated no survival advantage for patients choosing bilateral mastectomy.
Important Questions
These treatment and outcome patterns prompt several questions: What is motivating patients to pursue more extensive surgery than is actually necessary to address the known cancer? Are the motivating factors oncologically sound? And what are the public health implications of contralateral prophylactic mastectomy in terms of balancing health-care costs with addressing the burden of breast cancer?
Data from Hawley et al6 generated appropriate attention because these investigators found that contralateral prophylactic mastectomy patients were often motivated by the perception that they were achieving a survival or local recurrence advantage. Studies of outcome for unilateral vs metachronous bilateral breast cancer patients have historically demonstrated that survival tends to be driven by the stage and effectiveness of treatment for the initially detected cancer.7 This outcome equivalence is a biologically plausible observation, since unilateral breast cancer patients are typically receiving close surveillance and most second breast cancers will be detected at an early stage when they are likely to be successfully treated; the initially diagnosed breast cancer therefore has the lead-time advantage in establishing distant organ micrometastases.
Studies revealing surveillance equivalence for contralateral prophylactic mastectomy compared to no–contralateral prophylactic mastectomy patients8-10 are consistent with pathology studies revealing very low rates of incidentally detected cancers in the contralateral prophylactic mastectomy specimens.11 The data demonstrate that the procedure is extremely unlikely to be beneficial to our breast cancer patients from the perspective of eradicating an occult, preexisting contralateral malignancy.
Conflicting Evidence
On the other hand, some recent studies have demonstrated a survival advantage associated with the contralateral prophylactic mastectomy choice among unilateral breast cancer patients.12-14 This observation is also biologically plausible, in light of several related issues that affect outcomes to varying degrees as our treatment strategies evolve: first, a personal history of breast cancer is a risk factor for developing a new primary breast cancer; second, survival for most unilateral breast cancer patients is driven by the micrometastatic potential of their disease; and third, as effectiveness of systemic therapy for breast cancer has improved, we are likely seeing a larger pool of patients who have been “cured” of their initial breast cancer, and who might then be facing a significant life-threatening risk from a second/metachronous breast cancer.
It is therefore conceivable that contralateral prophylactic mastectomy might improve survival by reducing the incidence of new primary/metachronous disease. However, many of our systemic therapy agents are also effective in decreasing the incidence of contralateral breast cancer, thereby mitigating the potential for contralateral prophylactic mastectomy to confer an outcome advantage. Studies revealing a contralateral prophylactic mastectomy survival advantage are also confounded by selection bias,15 since unilateral breast cancer patients facing a diminished life expectancy because of advanced age, high-risk disease, or extensive comorbidity are less likely to undergo preventive surgery.
Other Motivations
Some patients may be motivated to pursue contralateral prophylactic mastectomy purely for body habitus and symmetry advantages. The patient with large pendulous breasts requiring mastectomy for unilateral disease may prefer to have a symmetrically flat chest wall (to avoid the sensation of torso imbalance or the need to be fitted for a large/heavy unilateral prosthesis) if she has medical contraindications precluding immediate reconstruction or contralateral reduction mammoplasty surgery. Patients with unilateral breast cancer undergoing reconstruction using an abdominal flap may opt for bilateral mastectomy/bilateral reconstruction because of the knowledge that the abdominal flap can only be harvested once, regardless of whether it is being utilized for unilateral or bilateral reconstruction.
Many unilateral breast cancer patients, even if fully cognizant of the data supporting survival equivalence for unilateral vs bilateral surgery, will continue to be motivated to pursue contralateral prophylactic mastectomy because of emotional reasons related to the risk-reducing benefits of this strategy. Often our breast cancer patients profess a clear desire to do anything possible in order to minimize the risk of repeating the breast cancer diagnosis and treatment experience, knowing that a second primary breast cancer would indeed warrant delivery of appropriate multidisciplinary care. In this scenario, the patient may feel that the goals of avoiding future chemotherapy and/or future axillary staging surgery may be worth the operative risks of undergoing more extensive surgery.
Surgeon’s Perspective
Surgeons can be subject to a comparable emotional component in the discussion of contralateral prophylactic mastectomy. Any surgeon with a substantial breast cancer patient population has had the heartbreaking experience of dealing with women who successfully battled their first breast cancer, only to be diagnosed with an aggressive/locally advanced or inflammatory contralateral breast cancer during long-term follow-up. These cases may defy the odds, but they nonetheless leave the patient and surgeon alike wondering whether contralateral prophylactic mastectomy might have been a lifesaving procedure when the first cancer was detected.
Along those same lines of speculation—but with the advantage of statistical support—there are also published decision-analysis studies regarding the cost-efficiency of contralateral prophylactic mastectomy. At least two of these studies suggest that contralateral prophylactic mastectomy may actually be comparable or preferable to long-term surveillance in unilateral breast cancer/unilateral breast surgery patients who have a particularly elevated risk of developing a new primary breast cancer, such as those with hereditary susceptibility.16,17
Furthermore, despite the preponderance of data supporting survival equivalence for unilateral vs bilateral mastectomy, individual surgeons know that the contralateral prophylactic mastectomy option is widely available in the health-care “marketplace.” They therefore feel obligated to include it in the spectrum of treatment strategies offered to the patient.
Clinical judgment for the safety of our patients is of course of paramount importance; surgeons are therefore also obligated to inform patients of the increased perioperative risks associated with bilateral surgery and that only medically fit patients should entertain this surgical option. Surgeons must take the time to clearly explain that the potentially life-threatening distant metastatic risk from the known cancer is unaffected by the choice of mastectomy vs breast-conserving surgery, and that recommendations for systemic therapy/chemotherapy are similarly unaffected by breast surgery choice. Nor does mastectomy surgery completely eliminate the risk of a local recurrence or of a new primary tumor, since the former is related to individual tumor biology and the latter can still occur as a function of microscopic foci of residual breast tissue left behind in the skin flaps or in the axilla.
Decision-Making Factors
As clearly shown by Kurian et al, breast-conserving surgery is comparable to mastectomy surgery with regard to survival and patients should bear in mind that breast-conserving surgery does not eliminate the option of pursuing more extensive mastectomy surgery for risk-reducing purposes in the future. Among patients for whom lumpectomy appears technically feasible, breast-conserving surgery may even be preferable to mastectomy in light of clinical trial data that document the safety of avoiding axillary lymph node dissection in lumpectomy/breast irradiation patients with limited-volume disease in the sentinel nodes.18
In contrast, mastectomy patients with sentinel node metastases will usually require completion axillary lymph node dissection in order to define the benefits of postmastectomy radiation. Furthermore, the node-positive mastectomy patient is often discouraged from undergoing immediate reconstruction, because of the potential risk for irreversible radiation damage to the reconstructed breast.
Encouraging our newly diagnosed breast cancer patients who are breast conservation candidates to pursue a methodical surgical plan initiated with sentinel lymph node biopsy (with or without a concomitant lumpectomy) can be a useful approach—this strategy provides valuable staging information without burning any bridges. If nodal metastases are identified, the patient may feel more comfortable with the lumpectomy/radiation option so that the morbidity of axillary lymph node dissection can be avoided. Breast conservation for the known disease then obviates the consideration of contralateral prophylactic mastectomy, although elective bilateral prevention surgery (with immediate reconstruction) remains an option after comprehensive cancer treatment is completed.
Empowering Patients
Facing a new breast cancer diagnosis is understandably a terrifying experience for our patients. The shock and mortality fears can have polar extreme effects—paralyzing some patients with indecisiveness and catapulting others into a tailspin of reflex preference for bilateral mastectomy because of the instinctive impression that the most aggressive surgery possible might be lifesaving. Thus far, however, a myriad of complex and conflicting theories and data inform the discussion of contralateral prophylactic mastectomy.
It is irrefutable that such surgery is increasing in the United States, but at this point in time the procedure does not appear to confer any definitive survival advantage. Prophylactic mastectomy is, however, a legitimate (albeit aggressive) strategy to reduce risk of a second primary breast cancer. Since a history of breast cancer is indeed a significant risk factor for developing a subsequent new primary tumor, we cannot summarily or paternalistically dismiss the contralateral prophylactic mastectomy option among our patients who express prevention as a personal priority.
As members of the cancer-treating team, we can empower our patients by underscoring the fact that although expeditious cancer treatment is important, they should not feel that they are racing the clock. As we educate our patients regarding the nature of their diagnosis and their treatment options, we must also encourage them to carefully process this information before hastily committing to irreversible surgical plans. ■
Disclosure: Dr. Newman reported no potential conflicts of interest.
References
1. Kurian AW, Lichtensztajn DY, Keegan TH, et al: Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. JAMA 312:902-914, 2014.
2. Newman LA: Understanding the reasonable, but limited benefits of the CPM strategy. Ann Surg 254:8-9, 2011.
3. Newman LA: Contralateral prophylactic mastectomy: Is it a reasonable option? JAMA 312:895-897, 2014.
4. Tuttle TM, Abbott A, Arrington A, et al: The increasing use of prophylactic mastectomy in the prevention of breast cancer. Curr Oncol Rep 12:16-21, 2010.
5. Tuttle TM, Habermann EB, Grund EH, et al: Increasing use of contralateral prophylactic mastectomy for breast cancer patients. J Clin Oncol 25:5203-5209, 2007.
6. Hawley ST, Jagsi R, Morrow M, et al: Social and clinical determinants of contralateral prophylactic mastectomy. JAMA Surg. May 21, 2014 (early release online).
7. Newman LA, Sahin AA, Cunningham JE, et al: A case-control study of unilateral and bilateral breast carcinoma patients. Cancer 91:1845-1853, 2001.
8. Kiely BE, Jenkins MA, McKinley JM, et al: Contralateral risk-reducing mastectomy in BRCA1 and BRCA2 mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Breast Cancer Res Treat 120:715-723, 2010.
9. Chung A, Huynh K, Lawrence C, et al: Comparison of patient characteristics and outcomes of contralateral prophylactic mastectomy and unilateral total mastectomy in breast cancer patients. Ann Surg Oncol 19:2600-2606, 2012.
10. Pesce C, Liederbach E, Wang C, et al: Contralateral prophylactic mastectomy provides no survival benefit in young women with estrogen receptor-negative breast cancer. Ann Surg Oncol 21:3231-3239, 2014.
11. King TA, Gurevich I, Sakr R, et al: Occult malignancy in patients undergoing contralateral prophylactic mastectomy. Ann Surg 254:2-7, 2011.
12. Peralta EA, Ellenhorn JD, Wagman LD, et al: Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer. Am J Surg 180:439-445, 2000.
13. Herrinton LJ, Barlow WE, Yu O, et al: Efficacy of prophylactic mastectomy in women with unilateral breast cancer: A cancer research network project. J Clin Oncol 23:4275-4286, 2005.
14. Boughey JC, Hoskin TL, Degnim AC, et al: Contralateral prophylactic mastectomy is associated with a survival advantage in high-risk women with a personal history of breast cancer. Ann Surg Oncol 17:2702-2709, 2010.
15. Kruper L, Kauffmann RM, Smith DD, et al: Survival analysis of contralateral prophylactic mastectomy: A question of selection bias. Ann Surg Oncol 21:3448-3456, 2014.
16. Zendejas B, Moriarty JP, O’Byrne J, et al: Cost-effectiveness of contralateral prophylactic mastectomy versus routine surveillance in patients with unilateral breast cancer. J Clin Oncol 29:2993-3000, 2011.
17. Roberts A, Habibi M, Frick KD: Cost-effectiveness of contralateral prophylactic mastectomy for prevention of contralateral breast cancer. Ann Surg Oncol 21:2209-2217, 2014.
18. Giuliano AE, Hunt KK, Ballman KV, et al: Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial. JAMA 305:569-575, 2011.
Dr. Newman is Professor of Surgery and Director of the Breast Care Center at the University of Michigan Comprehensive Cancer Center, Ann Arbor.
