Primary Prevention: Bilateral Risk-Reduction Mastectomy

The goal of bilateral risk-reduction mastectomy is to reduce the incidence of breast cancer in certain high-risk patients. To determine objective risk stratification, a complicated mix of familial and genetic factors, reproductive history, lifestyle options, and history of certain abnormality found on breast biopsies must be taken into account. Patients are provided information about the benefits and risks with regard to risk-reduction surgery. Rather than perform risk-reduction mastectomy for reason of speculative benefit, attention is now being directed toward establishing evidence-based data showing objective benefits for women demonstrated to be at elevated risks.

Initial stratification determines which patients should undergo further evaluation in addition to normal a history and physical examination. In the past, risk-reduction mastectomy had been performed for women with any family history, painful breasts, cancer phobia, or history of multiple breast biopsies. With significant advances in genetic screening and understanding of the molecular characteristics of breast abnormality, the current trend is to quantify risk and assess accordingly.

In a woman without a personal history of breast cancer, familial and genetic factors should be evaluated first. A full family history should be obtained, specifically discussing breast and ovarian abnormality. A formal referral to a genetic counseling specialist should be made if a patient has elevated risk based on family history. Further analysis for known genetic mutations such as the BRCA 1/2 (hereditary breast and ovarian cancer), TP53 (Li-Fraumeni syndrome), STK11 (Peutz-Jegher syndrome), PTEN (Cowden syndrome), and CDH1 (hereditary diffuse gastric cancer) genes may be assessed.

Multiple characteristics obtained during routine patient evaluation may indicate increased risk for breast cancer. Elevated levels of estrogens are associated with increased risk of breast cancer. Nulliparity, increased time between menarche and age of first live birth, and use of hormone therapy for treatment of the symptoms of menopause all increase risk. Furthermore, elevated body mass index, alcohol consumption, and tobacco consumption have all been associated with increased risks of breast cancer development. Last, women with a history of radiation therapy to the chest before age 30 are at elevated risk for the development of breast cancer.

With the growing understanding of the myriad risk factors, both modifiable and innate, more information about quantifying individual patient risks is possible. Much research has sought to quantify individual risk factors and attribute scores to categorize patients into risk levels. The 2 most commonly used scoring systems are those modified from the Gail and Claus models.

The 1989 publication from Gail and colleagues quantified the risk of developing breast cancer for groups of Caucasian women either under or over 50 years of age. A risk score was determined using age at menarche, age at first live birth, number of previous breast biopsies, and number of first-degree relatives with breast cancer. With the progress of genetic screening, specifics of molecular abnormality, and modifiable risk factors, multiple models have been proposed to most accurately assess individual risk. The National Cancer Institute’s Breast Cancer Risk Assessment Tool is a risk calculator based on an updated Gail model. It assesses a 5-year and lifetime risk score for women 35 years of age and older. It attempts to assess risk for multiple races of women and also addresses patient age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, number of previous breast biopsies, presence of atypical ductal hyperplasia on biopsy, race, mutation in BRCA 1/2 genes or other syndrome associated with increased breast cancer risk, history of ductal or lobular carcinoma in situ, and previous chest radiation for Hodgkin lymphoma. The contemporary Gail score continues to be important because US Food and Drug Administration guidelines for recommending discussion about surgical risk prevention and chemoprophylaxis are based on Gail score values.

We are still not able to predict who will get breast cancer and who will succumb to breast cancer regardless of risk factors. Further complicating matters is that the medical and surgical treatment of breast cancer has evolved significantly. In the 1990s, Ernster demonstrated that among certain high-risk patients, most of the women would not die from breast cancer. In the early 2000s, Roukas noted the incomplete penetrance of the BRCA mutation, at that time showing that 70% of gene carriers were affected. This data postulated that up to 30% do not have genetic penetrance and thus risk-reduction mastectomy would not be therapeutic. As diagnosis and treatment change, data reflecting incidence and mortality change as well.

In most practices, following the recommendations of the National Comprehensive Cancer Network (NCCN), the option of risk-reduction surgery is presented to patients with BRCA 1/2 or other predisposing gene mutation, strong family history of breast cancer, high-risk breast lesions like lobular carcinoma in situ (LCIS)/atypical ductal hyperplasia (ADH), or breasts difficult to survey. Multiple studies have shown a decrease in breast cancer incidence after bilateral risk-reduction mastectomy for both high-risk and moderate-risk women. In addition, many have shown a disease-specific morality decrease after risk-reduction surgery in this patient population. Further interpretation can extrapolate that 6 women at high risk need to undergo a risk-reduction mastectomy to prevent one case of breast cancer, and that 25 women at high risk would need to be treated to prevent one breast cancer death.

Although objective and quantifiable data are useful in making medical and surgical decisions, the psychological effect of confronting breast cancer must be taken into account. A woman who has seen a family member or friend struggle with breast cancer faces a looming cloud of uncertainty regarding how the disease may or may not affect her. As risk factors become known and risk score validity increases, a feeling of inevitable threat can profoundly impact patients’ lives. A patient’s understanding of her individual risk can be a large contributor to psychological health. Van Dijk and colleagues noted a significant decrease in perceived risk among women after counseling. Before education, most women believed they have risks much higher than their actual risk. This overestimation of risk was particularly significant for women at low risk, a population less likely to benefit from risk-reduction surgery. The discrepancy between actual and perceived risk is relevant in light of multiple studies showing that many women considering risk-reduction surgery made decisions based on an incorrect actual level of actual risk. Physician counseling is paramount in providing patients with all available information working together to determine appropriate treatment goals.

Recurrence Prevention: Contralateral Risk-Reduction Mastectomy

The goal of contralateral risk-reduction mastectomy is to reduce the risk of developing breast cancer in the contralateral breast of a woman previously diagnosed with unilateral breast cancer. Women with a personal history of carcinoma in one breast have an estimated risk of 0.5% to 1% per year of contralateral breast cancer. Although most data show contralateral risk-reduction mastectomy does decrease the incidence of contralateral breast cancer, insufficient evidence is present to show a decrease in breast cancer–specific mortality. Mortality is often dictated by metastasis of the index tumor. No improvement in disease-specific mortality is seen if the risk of mortality from metastasis of the index tumor is greater than the added mortality risk from contralateral breast cancer. The merits of the contralateral risk-reduction mastectomy are then based on the physical and emotional sequelae of diagnosis and treatment of a second cancer, not based on prolonging life.

A woman with a BRCA mutation has 56% to 87% lifetime risk of developing breast cancer. In a patient with unilateral breast cancer and a BRCA mutation, there is a 40% to 50% risk of developing a second primary breast cancer in the contralateral breast. It is generally accepted that options for contralateral risk-reduction mastectomy should be presented to women at high risk for contralateral breast cancer based on adaptations from the Society of Surgical Oncology’s recommendations. This group of women is characterized by having age at diagnosis less than 40 years, lobular histology of the primary breast cancer, strong family history, contralateral breast benign findings, difficult surveillance, reconstruction considerations, or genetic findings discovered after initial mastectomy. Barry and colleagues have also demonstrated multivariate analysis identifying invasive lobular histology, an ipsilateral multicentric tumor, and a 5-year Gail risk 1.67% as predictors of a contralateral malignancy.

After an initial breast cancer diagnosis, it is reasonable for a woman to have psychological anxiety related toward the possibility of developing breast cancer in the unaffected breast. In comparison to the psychological effects previously addressed regarding women who may pursue a bilateral risk-reduction mastectomy, women with unilateral breast cancer also have to assess the risks and benefits of operating on a breast without known abnormality. Where these patients differ is that they already have had one cancer diagnosis and are faced with the sequelae of neoadjuvant and adjuvant treatment. It can be daunting to imagine a second cancer diagnosis in the future and the thought of having to undergo treatment again. The fear of possible future cancer in the other breast potentially could sway a woman to pursue more operative intervention upfront in the hopes of avoiding a second breast cancer diagnosis.

What is clear is that women who thought they had an active role in decision making were twice as likely to be satisfied with contralateral prophylactic mastectomy when compared with patients who thought they were guided toward a decision or shared the decision-making process with the physician.