Is nipple-sparing prophylactic mastectomy (NSPM) effective in preventing breast cancer in high-risk individuals, particularly those with genetic mutations such as BRCA1 (Breast Cancer Gene 1) or BRCA2 (Breast Cancer Gene 2)?

Nipple-Sparing Prophylactic Mastectomy for Breast Cancer Prevention

Nipple-sparing prophylactic mastectomy (NSPM) is highly effective at preventing breast cancer in high-risk individuals, particularly BRCA1/2 mutation carriers, achieving at least 90% risk reduction with no breast cancers observed in multiple large series. 1

Evidence for Effectiveness

Prophylactic bilateral mastectomy, including nipple-sparing techniques, provides the most effective strategy available for breast cancer risk reduction in BRCA mutation carriers. 1 The evidence demonstrates:

• Risk reduction of at least 90% has been consistently shown with prophylactic bilateral mastectomy in BRCA carriers. 1
• In prospective studies, no breast cancers were diagnosed in the risk-reducing mastectomy group compared with 7-13% breast cancers in women under surveillance with mean follow-up of 3 years. 1

Specific Data on Nipple-Sparing Technique

The oncological safety of nipple-sparing mastectomy specifically has been validated through multiple high-quality studies:

• In a multi-institutional study of 548 risk-reducing NSMs in 346 BRCA carriers with median follow-up of 34 months, zero ipsilateral breast cancers occurred after prophylactic NSM, representing a statistically significant reduction compared to the 22 expected cancers without surgery (P < 0.001). 2
• A single-institution series of 307 BRCA1/2 carriers undergoing 607 NSMs showed no new cancers in 388 bilateral prophylactic cases over 744 cumulative woman-years of follow-up. 3
• Another series of 192 women undergoing 384 prophylactic NSMs showed no new breast cancer diagnoses after median follow-up of 36.8 months. 4
• A matched cohort study comparing 105 BRCA carriers who underwent NSM versus surveillance showed zero breast cancers in the NSM group versus 9 cancers in the surveillance group over mean follow-up of 50-58 months. 5

Guideline Recommendations

The NCCN Guidelines state that nipple-sparing mastectomy has been suggested to be a safe and effective risk reduction strategy for patients carrying a BRCA1/2 pathogenic or likely pathogenic variant, although more data and longer follow-up are needed. 1 This cautious language reflects the relatively shorter follow-up compared to total mastectomy, but the accumulating evidence is consistently favorable.

ESMO guidelines note that preliminary reports show similar failure rates with superior cosmetic results compared with other mastectomy techniques, though follow-up on this procedure is still short. 1

Important Caveats

Survival Benefit Not Yet Demonstrated

While risk reduction is clearly established, survival benefits have not been demonstrated with risk reduction breast surgery. 1 This is an important distinction—the procedure prevents cancer development but mortality benefit requires longer follow-up studies.

Follow-Up Duration Limitation

The main limitation across all studies is relatively short follow-up (median 34-50 months in most series). 2, 3, 4 Breast cancer risk in BRCA carriers extends throughout their lifetime, so longer-term data beyond 5-10 years would strengthen the evidence base. 1

Residual Breast Tissue Concern

Historically, total mastectomy has been considered the preferred standard because sparing the skin and nipple-areola complex could leave a substantial amount of breast tissue. 1 However, current surgical techniques appear to adequately address this concern based on the zero-event rates observed.

Clinical Application

Risk-reducing mastectomy should be discussed on a case-by-case basis with counseling regarding the degree of protection offered and the degree of cancer risk. 1 Key discussion points include:

• Age and life expectancy should be considered during counseling, as breast cancer risk remains increased with age in BRCA carriers. 1
• Multidisciplinary consultations are recommended before surgery and should include discussions of the risks and benefits of surgery and surgical breast reconstruction options. 1
• Immediate breast reconstruction is an option for many women following risk-reducing mastectomy, and early consultation with a reconstructive surgeon is recommended. 1

Psychosocial Considerations

A 2018 Cochrane review showed that patients are generally satisfied with their decision, with reported decreases in worry about breast cancer, but negative impacts on body image and sexuality have also been reported. 1 Long-term physical symptoms such as lower sensitivity to touch, pain, tingling, infection, and edema are also associated with the procedure. 1