APPENDIX II: PROPHYLACTIC MASTECTOMY

Stephen B. Edge, MD

Prophylactic mastectomy is one option for intervention considered by some women at defined high breast cancer risk.^1,2,3,4 Most authors believe that the option of prophylactic mastectomy should be available to women in families with apparent inherited breast cancer high risk, and those who by genetic testing are determined to carry mutations in breast cancer associated genes (e.g. BRCA1, BRCA2). The use of any prevention strategy such as prophylactic mastectomy depends on 1) identifying the individual at high-risk, and 2) demonstrated efficacy of the intervention.

A specific level of risk sufficient to justify prophylactic mastectomy cannot be set. Ultimately, the decision to undergo this treatment rests with the individual, assuming that accurate, unbiased information is provided with sufficient time and patience to allow a truly informed decision. All authors agree that prophylactic mastectomy is never an urgent procedure and most argue for at least a six month period of discussion, counseling and contemplation.

Outside the setting of a known carrier of genetic predisposition to breast cancer, risk is quantified by mathematical models incorporating known risk factors (e.g. the models of Gail and Claus). Most authors conclude that prophylactic mastectomy is not indicated for women without quantifiable high-risk. In the past, it was often performed for reasons such as chronic mastalgia, "fibrocystic disease" and cancer phobia. It is now generally limited to women with known high risk by virtue of strong family history and/or findings on breast biopsy known to increase risk of future invasive cancer (atypical hyperplasia, lobular carcinoma in situ). In 1993, the Society of Surgical Oncology published a position statement on situations where it is reasonable to consider prophylactic mastectomy.⁵ These encompassed prophylactic bilateral mastectomy for women at high risk and prophylactic contralateral mastectomy for women with a prior breast cancer.

The degree of reduction of risk of breast cancer with prophylactic mastectomy is not well documented in the literature. It is clear that no surgical technique for prophylactic mastectomy removes all breast epithelium. The two techniques used are "subcutaneous mastectomy" and "total mastectomy". Subcutaneous mastectomy removes the breast tissue leaving the nipple/areolar complex intact in order to preserve appearance and nipple sensation. Approximately 10-20% of the breast epithelium remains under the areola after subcutaneous mastectomy. Because a significant proportion of breast tissue is left with the nipple by subcutaneous mastectomy, this operation is generally not indicated if mastectomy is to be done for breast cancer prevention. Total mastectomy including nipple removal is necessary to remove the maximum amount of breast tissue. However, at least microscopic deposits of breast epithelium remain on all the skin flaps and pectoralis muscle.⁶ The surgical dissection should include: 1) dissection of thin cutaneous flaps, 2) extension of the flaps to the clavicle superiorly, sternum medially, upper border of the rectus abdominis muscle inferiorly, and latissimus dorsi muscle laterally, and 3) complete removal of the axillary tail of Spence, obliging removal of some low axillary lymph nodes.

Breast cancer has been reported to occur in followup after all types of prophylactic mastectomy, including total mastectomy, with the first case report in the mid 1960's. There are a number of oft-quoted animal studies which demonstrate no reduction in the number of carcinogen-induced mammary cancers by surgical removal of breast tissue. Obviously the relevance of these animal studies to human breast cancer is uncertain.

The existing literature on breast cancer risk after prophylactic mastectomy is scanty^7,8,9,10. The data consist of retrospective surveys of physicians and patients. These studies are weakened by their retrospective nature, variability in surgical technique, short and variable duration of follow-up, loss of women to follow-up, and limited information on breast cancer risk factors in treated women. By necessity, all such retrospective studies examine the outcome of women treated in the 1960's and 1970's. This time period predated the current level of understanding of breast cancer risk factors and the quantitative models of Gail and Claus published in the late 1980's. Detailed risk factor data and three generation family histories are not available and many women in these series had prophylactic mastectomy for indications such as dense breasts, mastalgia, fibrocystic disease and cancer phobia.

The available studies are summarized in Table I. 0.2% - 1% of women developed invasive breast cancer after prophylactic mastectomy. In two studies where breast cancer risk factors could be evaluated to some extent, breast cancer after prophylactic mastectomy occurred in 1% and 19% of high-risk women, based on six and three cases respectively.

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"Table I: Studies of Prophylactic Mastectomy"

The best documented study included 1500 women, of whom 510 were "high-risk". 6/510 developed breast cancer with a median nine year follow up. It is not possible to determine the true risk of cancer for these women had they not had prophylactic mastectomy. Therefore, the level of risk reduction by surgery is unknown. A third study recently published in abstract form evaluated the risk of breast cancer after prophylactic mastectomy.¹¹ A cohort of 1125 who underwent a prophylactic bilateral mastectomy completed a family history questionnaire. Of these, 580 had a family history, and 203 had a family history suggestive of a single gene inherited trait. Overall seven women developed breast cancer with an average 17 year follow-up, five of which occurred in women with a family history. Compared to age-adjusted SEER incidence rates and Gail model risk analysis, the reduction of breast cancer risk by prophylactic mastectomy was estimated as 91%. Other retrospective cohort studies are in progress. Ultimately, prospective registry studies on known carriers of breast cancer-associated gene mutations who undergo prophylactic mastectomy will be needed to answer this question.

CONCLUSIONS:

1. Prophylactic mastectomy appears to reduce but not eliminate breast cancer risk. The degree of risk reduction, especially for gene carriers, is unknown.

2. When prophylactic mastectomy is performed, the operation should be total mastectomy with removal of the nipple/areolar complex.

3. Prospective study through registries of women who undergo prophylactic mastectomy is necessary. However, answers from these studies will be many years away because of the long follow up necessary.

4. Women considering prophylactic mastectomy should be carefully counseled about breast cancer risk, morbidity and mortality, the long term medical and psychological consequences of surgery, and alternatives to surgery.

References:

1. Lopez MJ, Porter KA: The current role of prophylactic mastectomy. Surgical Clinics of North America. 1996; 76(2):231-42.

2. Ziegler LD, Kroll SS: Primary breast cancer after prophylactic mastectomy. Am J Clin Oncol (CCT) 1991; 14(5):451-4.

3. Stefanek ME: Bilateral prophylactic mastectomy: Issues and concerns. Monogr Natl Cancer Inst 1995; 17:37-42.

4. Wapnir IL, Rabinowitz B, Greco RS: A reappraisal of prophylactic mastectomy. Surg Gynecol Obstr 1990; 171:171-84.

5. Society of Surgical Oncology: SSO develops position statement on prophylactic mastectomies. SSO News. Summer 1993;1:10.

6. Temple WJ, Lindsay RL, Magi E, Urbanski SJ: Technical considerations for pro-phylactic mastectomy in patients at high-risk for breast cancer. Am J Surg 1991; 161:413-5.

7. Humphrey LJ: Subcutaneous mastectomy is not prophylaxis against carcinoma of the breast: Opinion or knowledge? Am J Surg 1983; 145:311-2.

8. Bohmert HH: Subcutaneous mastectomy. In: Grundfest-Broniatowski S, Esselstyn BC Jr. Eds. Controversies in breast disease: diagnosis and management. New York: Marcel Dekker, 1988; 235-59.

9. Woods JE: Breast reconstruction: current state of the art. Mayo Clin Proc 1986;
   61:579-85.

10. Pennisi VR, Capozzi A: Subcutaneous mastectomy data: a final statistical analysis of
    1500 patients. Aesthetic Plast Surg 1989; 13:15-21.

11. Hartmann LC et al. Prophylactic mastectomy: Preliminary retrospective cohort
    analysis (abstr). Proc Amer Assoc Cancer Res 1997; 38:168