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
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
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.
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.
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