VIDEO: Inside Angelina Jolie's Double Mastectomy Decision * 2023
VIDEO: Inside Angelina Jolie's Double Mastectomy Decision * 2023

Prophylactic mastectomy for the prevention of breast cancer

Also called mastectomy, elective. The use of prophylactic bilateral and contralateral mastectomies is steadily increasing in the United States. Prophylactic mastectomy can be bilateral in healthy women at high risk of breast cancer, or unilateral if performed for a non-invasive breast lesion or in addition to a therapeutic mastectomy in the contralateral breast.

The rate of prophylactic mastectomy in women at high risk of breast cancer had increased during the years between 2004 and 2008 to reach 35.7% for bilateral mastectomy and 22.9% for contralateral mastectomy.

Prophylactic mastectomy could be technically performed in different ways. Total mastectomy (also called simple mastectomy) is a procedure in which most of the breast tissue, including the nipple-areola complex, is removed through an elliptical skin incision, but the muscle tissue beneath the breast is spared and the axillary lymph nodes. It is unlikely that all breast tissue will be eradicated; although, all visible breast tissue is removed.

Some breast tissue may unintentionally remain under the skin, in the inframammary fold, or near the armpit fat pad. In addition to total mastectomy, skin-sparing mastectomy is a way to remove breast tissue, including the nipple-areolar complex, through a periareolar incision, leaving most of the skin over the breast intact. This facilitates reconstruction and the skin of the breast is preserved without scars. As an extension of skin-sparing mastectomy, nipple-sparing mastectomy (also called total skin-sparing mastectomy) preserves the nipple-areolar complex and the skin over the breast. This is usually accomplished through an inframammary incision where the skin is carefully dissected from the breast until all anatomical limits of the breast are reached and the breast is removed in its entirety. It is important to avoid leaving breast tissue behind the nipple-areola complex.

This process is technically demanding and requires a lot of effort to reach the deepest limits of the breast through a small, deep incision. Specific retractors with light sources can be used to facilitate excision. Historically, skin-sparing mastectomy was more often preferred than total mastectomy. Today, total mastectomy is the preferred prophylactic procedure, due to the advantage of current nipple reconstruction techniques. Skin-sparing mastectomy was preferred more frequently than total mastectomy. Today, total mastectomy is the preferred prophylactic procedure, due to the advantage of current nipple reconstruction techniques. Skin-sparing mastectomy was preferred more frequently than total mastectomy. Today, total mastectomy is the preferred prophylactic procedure, due to the advantage of current nipple reconstruction techniques.

The increasing rate of postoperative complications, in addition to the doubtful oncological safety of nipple-sparing mastectomy, generated reluctance among some institutions and surgeons to adopt this technique. In general, there is still debate about the most appropriate type of mastectomy for high-risk women, and it should be selected carefully.

Impact of bilateral prophylactic mastectomy on breast cancer incidence

BRCA

In BRCA gene mutation carriers, several studies showed a significant reduction in the incidence of breast cancer in women who underwent bilateral prophylactic mastectomies. In 2001, Meijers-Heijboer  et al . conducted a prospective cohort study of 139 women carrying mutations in the BRCA1 or 2 gene. Seventy-six (55%) of these women underwent prophylactic bilateral simple mastectomy, while the other 63 (45%) women remained under surveillance. . As a result of a mean follow-up period of 2.9 years, none of the 76 women who underwent prophylactic mastectomy developed breast cancer, compared with 8 cases of breast cancer diagnosed in the surveillance group (proportion of cases observed to expected, 1.2; 95 % confidence interval, 0.4–3.7). In the same year, Hartmann et al. . They identified 26 women with a BRCA1 or 2 gene mutation from their previous retrospective cohort study of bilateral prophylactic mastectomies. None of the patients developed breast cancer during a median follow-up of 13.4 years after prophylactic mastectomies. Using two models, these studies show an 85% to 100% risk reduction achieved by prophylactic mastectomy. Furthermore, in 2004, Rebbeck et al. .[] conducted a prospective cohort study of 483 women from the same risk group.

One hundred and five of these women who underwent bilateral prophylactic mastectomy were compared with 378 controls who did not undergo prophylactic surgery. With a mean follow-up of 6.4 years, breast cancer was found in two patients (1.9%) in the bilateral prophylactic mastectomy arm and in 184 (48.7%) in the matched control arm, confirming a reduction 90% to 95% in breast Cancer risk after bilateral prophylactic mastectomy. In a recent large prospective cohort study, Domchek  et al. ] evaluated the relationship between prophylactic mastectomy and breast cancer outcomes in carriers of mutations in the BRCA1 and 2 genes. No breast cancers were observed in 257 women who underwent bilateral prophylactic mastectomy compared with 7% of women without surgery during the 3 years of follow-up, showing a decreased risk of breast cancer in carriers of BRCA1 and 2 gene mutations associated with bilateral prophylactic mastectomy . Additionally, in a 2015 study, 63 women carrying the BRCA1 or 1 gene mutation who underwent prophylactic nipple-sparing mastectomy reported no newly diagnosed breast cancers at a median follow-up of 26 months, supporting the same conclusion.[

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Abstract

The high incidence and recurrence rate of breast cancer has influenced multiple strategies such as early detection with imaging, chemoprevention, and surgical interventions that serve as preventive measures for high-risk women. Prophylactic mastectomy is one of the growing breast cancer risk reduction strategies that is especially important for carriers of breast cancer genetic mutations. Women with a personal history of cancerous breast lesions may also consider ipsilateral or contralateral mastectomy. Existing data showed that mastectomy effectively reduces the risk of breast cancer. However, careful risk estimation is necessary to wisely select people who will benefit from breast cancer prevention.

Breast cancer remains the most common cancer in women

With an annual incidence of 252,710 cases in the United States, resulting in 41,070 deaths, second only to lung cancer. The prevalence in 2014 had reached 3,346,387 cases, with a 12.4% probability of a woman being diagnosed with breast cancer during her lifetime, which increases with her age. According to the Surveillance, Epidemiology, and End Results (SEER) database, there has been a change in the incidence of breast cancer between the years 1975 and 2014. The annual percentage changes reported in the years 1975–1980 and 2004–2014 were , −0.5 and 0.3, respectively.

The increase in breast cancer incidence during the 1980s may be explained by changes in female reproductive patterns and the adoption of more aggressive screening techniques that have led to increased detection of the disease. The risk factors for developing the onset or recurrence of breast cancer are multiple and complex, including family history, genetic mutations, lifestyle, radiation exposure, parity, previous history, etc. Clinical characteristics and the type of primary cancer treatment may affect the risk of recurrence as well. Generally, the recurrence rate is highest in the first few years after the initial breast cancer diagnosis and then decreases.

Multiple strategies have been implemented to reduce the risk of breast cancer onset and recurrence. These interventions include lifestyle modification, early detection with imaging, chemoprevention, and surgical intervention. Prophylactic mastectomy is one of the growing strategies for breast cancer risk reduction. In this review, we will discuss the current evidence on prophylactic mastectomy in terms of types, indications, and its role in breast cancer prevention.

High risk population

Breast cancer risk assessment is based on both endogenous and exogenous factors. Mutations affecting known genes, compelling family history, benign breast diseases with specific histological features, history of breast cancer, or radiation therapy to the breast increase the risk of developing breast cancer. Familial susceptibility to breast cancer accounts for <25% of all breast cancer cases. Several genes have been implicated in familial cases. Mutations in the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes explain ~20% of familial clustering of breast cancer. BRCA1 is a tumor suppressor gene mapped to chromosome 17. Its protein product is part of a complex compound responsible for repairing double-strand breaks in deoxyribonucleic acid (DNA) that contribute to genomic instability and drive cancer development.

These ruptures can be induced by exposure to radiation or chemotherapy. The BRCA2 gene is located on chromosome 13 and has a similar function to the BRCA1 gene.  These genes are important for genome stability. The predisposed subject carries a defective allele of a tumor suppressor gene. Meanwhile, a second hit, the loss of the second copy of the gene, is a necessary step to trigger the growth of tumor cells. Therefore, women carrying BRCA1 or 2 gene mutations are thought to have a significantly increased risk of developing breast cancer, usually diagnosed at a younger age compared to the general population. The average cumulative risk of breast cancer at age 70 is estimated to be 57% to 65% for BRCA1 mutation carriers and 45% to 49% for BRCA2 mutation carriers. a 20-fold increase in the risk of breast cancer compared to the general population.  Similarly, mutations in other genes account for only a small fraction of familial cases. The p53 gene is located on chromosome 17 and, like BRCA, is a tumor suppressor gene. Mutations in this gene are found in 50% of all cancers. They are associated with a high lifetime risk of cancer and are involved in 1% of hereditary breast cancer cases.

The absolute lifetime risk of breast cancer in p53 gene mutation carriers is estimated to be 24%.  The phosphatase and tensin homologous gene (PTEN) located on chromosome 10 is widely expressed throughout the body. Regulates the cell cycle and triggers apoptosis. Mutations in this gene are the basis of several tumor syndromes: Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Proteus and Proteus-like syndromes. These syndromes increase the risks of several types of cancer, with female breast cancer being the highest.  The absolute lifetime risk of breast cancer for PTEN mutation carriers is estimated to be 25%.[ ] Aside from familial susceptibility, sporadic cases that do not show familial clustering are primarily due to the accumulation of rare mutations. penetrants in several genes affected by environmental factors. In general, genetic mutations are considered high risk for developing breast cancer when they show a 4-fold increased risk of breast cancer in carriers compared to the general population. Some benign breast diseases have been reported to increase the risk of subsequent development of breast cancer. Notably, the risk is higher with proliferative diseases than with nonproliferative histological changes. A cohort of 4970 women with biopsy-proven benign breast diseases was retrospectively studied to determine the subsequent development of breast cancer. The estimated overall incidence rate of breast cancer was 452/100,000 person-years at risk. Age >50 years increased the risk by 80%. The risk of breast cancer was significantly higher in women with proliferative lesions, with an incidence rate of 1.7, reaching 5.0 in atypical ductal hyperplasia (ADH).

Similarly, the relative risk associated with non-proliferative lesions was estimated at 1.28, compared to 1.88 for proliferative lesions and 4.24 for atypia. However, women with nonproliferative lesions and a negative family history did not show an increased risk.  The results of two other studies are consistent with the previous study and show comparable risk estimates ranging from 1.6 to 1.9 for women with proliferative disease without atypia and 3.7 to 5.3 for atypical hyperplasia, all in comparison with women who have non-proliferative lesions. They also reported an elevated risk related to calcification in proliferative lesions and in premenopausal women with atypical hyperplasia.  The estimated 10-year cancer risks were 17.3% with ADH, 20.7% with atypical lobular hyperplasia, 23.7% with lobular carcinoma  in situ  (LCIS), and 26% with severe ADH.  In addition to benign breast diseases, ductal carcinoma  in situ  (DCIS) is a non-invasive breast cancer composed of malignant epithelial cells completely delimited by a basement membrane of breast ducts, which normally does not metastasize to lymph nodes. The proportion of DCIS is around 20% of breast cancers detected by screening and carries a higher risk of developing invasive disease.

In one study, low-grade DCIS was found to have a 9-fold increased risk of developing cancer at the same time, within 30 years of diagnosis (95% confidence interval, 4.7–17) . The final diagnosis of a group of 241 women who underwent mastectomy after a preoperative biopsy showing DCIS revealed that 14% of the patients had microinvasive carcinoma, and 21% had invasive ductal carcinoma. In a previous study, it was reported that 26% of patients were found to have invasive disease. Another similar study showed comparable results.  Previous studies identified predictors correlated with infiltration and all were consistent in palpable tumor and large DCIS. . Early thoracic radiation before age 30 is a significant risk factor for breast cancer.

The Late Effect Study Group trial reported a 56.7-fold increased overall risk of breast cancer related to prior mantle radiation therapy at a young age compared with the general population. Women treated for unilateral breast cancer have an increased risk of developing contralateral breast cancer, with a 5-fold higher incidence of new cancer compared to the general population . 

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