Current Status of Prophylactic Mastectomy
Current Status of Prophylactic Mastectomy
Ghosh and Hartmann present an excellent overview on the risk reduction that prophylactic mastectomy offers the high-risk patient. Dr. Hartmann and the Mayo Clinic remain leaders in this field. As cited in their recent series, the risk of developing breast cancer is reduced 89.5% to 100% in high-risk women who choose to undergo prophylactic mastectomy. In the same year, Meijers-Heijboer et al supported these findings, documenting a 100% relative risk reduction. The fact that prophylactic surgery offers a dramatic reduction in the risk of breast cancer to high-risk patients appears unquestionable.
Ghosh and Hartmann present the current treatment options and summarize the data in a concise, easy-to-read table. Table 2 in their article shows that the relative risk reduction associated with tamoxifen chemoprevention is 49%, although the absolute risk reduction is 1.3% over 5.75 years. The absolute risk reduction does not appear as dramatic as the often quoted 49% relative risk reduction, but it needs to be understood and is clearly presented in this article.
The recently reported National Surgical Adjuvant Breast and Bowel Project’s P1 study has produced similar findings. No reduction in risk was identified among BRCA1 mutation carriers, because only five breast cancers were detected in the tamoxifen group and three in the placebo group. However, a headline-grabbing 62% relative-risk reduction was noted among BRCA2 carriers. This was based on 11 breast cancer cases8 detected in the placebo arm and 3 in patients receiving tamoxifen.Relative vs Absolute Risk
As noted in Ghosh and Hartmann’s review, three choices exist for the patient at high-risk for breast cancer: close surveillance, prophylactic surgery, and/or chemoprevention. The decision to pursue a particular therapy remains an extremely personal one. Once an individual’s risk of developing a primary or second breast cancer is estimated, it must be conveyed to the patient, as well as the reduction in risk that can be expected with current treatment strategies. Only then can the patient make an educated decision.
Physicians often quote the relative risk reduction to patients, although the absolute risk reduction is typically more relevant clinically. Is it appropriate to tell a patient with a Gail model score > 1.66 that her risk of breast cancer is decreased by 50% with tamoxifen? Would it not be more relevant to explain that her risk is 2.6% without tamoxifen and 1.3% with tamoxifen? Indeed, the same relative risk could be quoted when the patient’s risk is reduced from 100% to 50% or from 0.50% to 0.25%, but the first of these extreme examples is more clinically relevant to an individual patient. Given the second example, it would certainly not be worth accepting the associated toxicities of the medication.Indications for Prophylactic Mastectomy
The authors note that prophylactic mastectomy is a risk-reducing strategy for patients at high risk for breast cancer. However, many women overestimate their individual risk and many physicians overestimate the risk reduction provided by chemoprevention. The authors nicely summarize the risk reduction associated with different approaches.
Specific indications for prophylactic mastectomy were not addressed in this article. Certainly, the procedure should be considered in patients with BRCA mutations. Other indications are relative and need to be individualizedfor example, young age at diagnosis, strong family history without a known genetic mutation, lobular carcinoma in situ, mastectomy with reconstruction for contralateral carcinoma, multiple previous biopsies with dense breast tissue and difficult-to-interpret mammograms, cancer phobia, and cosmesis. In considering relative indications such as these, the best individual decision can only be made when the patient understands her true, as opposed to her perceived, risk of breast cancer.
Often, a genetics counselor can help the patient understand her genetic predisposition. Sometimes a psychiatric evaluation is also necessary prior to proceeding with surgical intervention, especially in the patient with severe cancer phobia regardless of the actual risk.Sentinel Lymph Node Biopsy
Prophylactic mastectomy is typically performed using a skin-sparing simple mastectomy technique with immediate reconstruction. At the H. Lee Moffitt Cancer Center, all patients scheduled for prophylactic mastectomy undergo lymphatic mapping and sentinel lymph node biopsy. We previously reported our results on the role of sentinel lymph node biopsy in women scheduled for prophylactic mastectomy, and here we present an update.
Over a 91-month period, 2,790 patients underwent lymphatic mapping for breast cancer. During this same period, we performed prophylactic mastectomies in 167 patients. Carcinoma was discovered within the removed breasts of seven patients (4.2%). Five of these tumors were infiltrating ductal carcinoma, and two were ductal carcinoma in situ. The sentinel node was negative for malignancy in six of these patients, and one patient had positive cells within the lymph node by immunhistochemical staining for cytokeratin (CK-IHC).
Our rate of incidental breast cancer found at the time of prophylactic mastectomy is equivalent to that reported in the literature (approximately 5%). Performing lymphatic mapping and sentinel lymph node biopsy at the time of surgery has the advantage of sparing the patient the morbidity of a complete axillary lymph node dissection during a second surgical procedure when an incidental carcinoma is detected.
Seven patients, six of whom were not found to have a cancer in the prophylactic mastectomy breast, had a positive sentinel node by CK-IHC staining. Thus 7.8% (13/167) of our patients had a significant finding at the time of prophylactic mastectomy as a direct result of sentinel lymph node biopsy (six incidental breast cancers, six CK-IHC cells in the sentinel node, and one patient with an incidental cancer and CK-IHC nodal involvement). This was accomplished with no increased morbidity from the biopsy.Conclusions
Patients are faced with a mounting body of information that can confuse decisions regarding treatment options for high-risk situations. The best decision can only be made once the patient’s breast cancer risk and the absolute risk reduction associated with a current therapy is known. Gosh and Hartmann present a complete and up-to-date review of the treatment options and their respective risk reductions, and make a compelling argument for prophylactic mastectomy as a definitive method of risk reduction.
1. Hartmann LC, Sellers TA, Schaid DJ, et al: Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 93:1633-1637, 2001.
2. Meijers-Heijboer HB, van Geel, van Patten WL, et al: Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 345:159-164, 2001.
3. Fisher B, Costantino JP, Wickerham DL, et al: Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371-1388, 1998.
4. King MC, Wieand S, Hale K, et al: Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286:2251-2256, 2001.
5. Dupont EL, Kuhn MA, McCann C, et al: The role of sentinel lymph node biopsy in women undergoing prophylactic mastectomy. Am J Surg 180:274-277, 2000.