1/8 American woman develop breast cancer.
Most women diagnosed with breast cancer have no significant risk factors.
There are many risk factors for breast cancer.
The most common risk factors increase risk slightly. It is unlikely that women with these risk factors alone would be considered “high risk” as pertains to our discussion:
Race: Caucasian women are at the highest risk, followed by African American women.
Lifestyle: elevated BMI, moderate to heavy alcohol use, and the use of combination estrogen-progesterone hormone replacement therapy (HRT).
Prolonged estrogen exposure due to early menarche (younger than 12) or late menopause (older than 55).
Increased mammographic breast density.
Age of first pregnancy: Women who are nulliparous or whose first pregnancy occurred at age 30 or later have double the risk of women whose first pregnancy occurred prior to age 20.
Breastfeeding is associated with a small reduction in risk.
Other risk factors are less common but may significantly increase a woman’s likelihood of developing breast cancer (ie, a strong family history, a known genetic mutation, or a history of atypia, lobular carcinoma in situ, or of mantle radiation), and women with these risk factors frequently are categorized as “high risk.”
Risk assessment for breast cancer has been important when ordering screening breast MRI. In fact, the main purpose of most of these models was to obtain insurance authorization for this screening modality. However, things are changing. Risk assessment is critical in lieu of new breast density legislation. Breast density is not a risk factor in and of itself, however, combined with risk assessment is critical in identifying individuals who are at higher risk, thus requiring high risk screening.
Patients with a known genetic mutation (see Hereditary Breast Cancers, above) or those who received mantle radiation at a young age are clearly at a high lifetime risk of developing breast cancer, but these patients are the minority. (Ref. 27-28)
For patients with a family history of breast cancer or with atypia or LCIS, risk assessment models can better quantify risk.
Risk assessment models incorporate various patient factors and family history and provide an estimation of a patient’s risk of developing breast cancer.
None of these models is perfect.
None of these models incorporates a history of mantle radiation.
The most commonly used risk assessment model.
Originally described in 1989 and revised in 1999.
Incorporates patient age, age of menarche, age of first pregnancy, history of prior breast biopsies, previous diagnosis of atypia, and number of first-degree relatives with breast cancer.
Age at cancer diagnosis is not considered.
Affected second- and third-degree relatives are not considered.
Not validated for women under 35 or for women with LCIS.
Women with a 5-year risk of >1.7% are considered high risk (1.7% is the average risk of a 60-year-old woman being diagnosed with breast cancer).
Risk based solely on family history (including non-first-degree relatives) of breast and ovarian cancer and incorporates the age of diagnosis in those family members.
No personal or hormonal factors are included.
Estimates the likelihood of a patient having a BRCA mutation and provides an estimate of that patient’s risk of breast or ovarian cancer.
Incorporates the number of affected and unaffected family members and includes male breast cancer.
Non-BRCA genetic mutations are not addressed.
No personal or hormonal factors are included.
Tyrer-Cuzick Model (IBIS Model [International Breast Cancer Intervention Study])
Estimates a patient’s risk of breast cancer and of having a BRCA mutation or of having another autosomal dominant breast cancer gene.
Incorporates personal and hormonal factors as well as extended family history of both breast and ovarian cancer.
BOADICEA Model (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm)
Predicts BRCA mutation likelihood and the risk of breast or ovarian cancer based on family history.
Family history includes breast, ovarian, prostate, and pancreatic cancers.
Two studies directly compared the accuracy of these multiple models:
Tyrer-Cuzick was found to be more accurate, based on ROC curve, than BRCAPRO and Gail Models
These latter 2 models were found to underestimate breast cancer risk
Tyrer-Cuzick and BOADICEA were found to be more accurate than Gail or Claus Models, as Gail and Claus underestimated breast cancer risk
Women estimated to have a lifetime risk of breast cancer of at least 20% are considered high risk.
Risk-reducing strategies such as the use of chemoprophylactic agents should be discussed with women whose estimated risk of breast cancer is 20% or greater.
Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs) and are FDA-approved as risk-reducing agents.
Tamoxifen (Ref. 42)
NSABP P-1 documented the efficacy of tamoxifen as a risk-reducing agent.
Tamoxifen (20 mg daily for 5 years) decreased the risk of developing invasive breast cancer by 49% and reduced the risk of developing noninvasive cancer by 50% in high-risk women.
Preventative effect of tamoxifen was limited to estrogen receptor (ER) positive tumors.
Associated with an increased risk of endometrial cancer and of thromboembolic events, most significantly in postmenopausal women.
Raloxifene (Ref. 43-44)
STAR Trial (NSABP P-2) compared tamoxifen and raloxifene.
Risk reduction for invasive cancer was similar between tamoxifen and raloxifene.
There was a lower risk of noninvasive cancer in the tamoxifen group, but this was not significant.
Lower risk of thromboembolic events
Not associated with the increase in cataracts seen with tamoxifen
Raloxifene positively affects bone density
Only FDA-approved for use in postmenopausal women and is dosed at 60 mg daily
No ideal length of treatment established
There is little or no evidence regarding the utility of chemoprophylaxis in women treated with mantle radiation or in women under 35.
There is limited evidence regarding the utility of chemoprophylaxis in women with BRCA1 and BRCA2 mutations.
Contraindications to these drugs include history of deep venous thrombosis, transient ischemic attack, thrombotic stroke, hypercoagulability, and pregnancy.
Common side effects of the SERMs include vasomotor symptoms, such as hot flashes.
An aromatase inhibitor currently used in the treatment of invasive breast cancer
Not yet FDA-approved as a risk-reducing drug
Recently published data on the MAP .3 Trial demonstrated a 65% risk reduction at 3 years follow-up in invasive breast cancer in high-risk postmenopausal women
Additional studies are ongoing
Prophylactic Risk-Reducing Surgery
Prophylactic mastectomy reduces risk by at least 90% in high-risk women, including those with BRCA mutations.
Prophylactic mastectomy is reasonable in women without a cancer diagnosis but with:
A known BRCA1 or BRCA2 mutation or with another known breast cancer susceptibility gene
A strong family history (ie, multiple family members affected, multiple generations affected, male breast cancer, premenopausal breast cancer, bilateral breast cancer)
A history of atypia or LCIS
Prophylactic oophorectomy in women with BRCA1 and BRCA 2 mutations reduces breast cancer risk by half.
Mutations associated with breast, ovarian, and pancreatic cancers
Estimated lifetime risk of breast cancer 39-87%
Mutations associated with breast, ovarian, pancreatic, and prostate cancers
Estimated lifetime risk of breast cancer 31-84%
Other less common hereditary breast cancers
PTEN gene mutation (Cowden syndrome)
25-50% estimated lifetime breast cancer risk
Associated with cerebellar ataxia, craniomegaly, facial trichilemmomas, oral mucosal papillomas, hamartomas, thyroid cancer, endometrial carcinoma, and other genitourinary cancers
P53 mutation (Li-Fraumeni syndrome)
90% estimated lifetime breast cancer risk, 56% by age 45
Associated with soft tissue sarcoma, osteosarcoma, brain tumor, adrenocortical carcinoma, Wilms tumor, phyllodes tumor, neuroblastoma, pancreatic cancer, and leukemia
STK11 mutation (Peutz-Jeghers syndrome)
31% risk of breast cancer by age 60
Associated with small intestine cancer, colorectal carcinoma, pancreatic carcinoma, and ovarian tumors
CDH1/E Cadherin mutation (Hereditary Diffuse Gastric Cancer)
39% lifetime risk of breast cancer
These are lobular breast cancers and are associated with diffuse gastric cancer.
For women with a 5-year estimated risk of >1.7% or a lifetime estimated risk of >20%, the following surveillance is recommended:
Annual screening mammography
Clinical breast exam every 6–12 months
Consider the addition of annual screening MR
In our practice, when we include annual MRI into a patient’s screening regimen, we stagger the annual mammogram and the annual MR by 6 months so the patient is undergoing some form of imaging every 6 months.
For women with a known genetic predisposition to breast cancer (eg, a BRCA mutation), the following is recommended:
Annual clinical breast exam for women under 25
Starting at age 25, annual mammography and annual MR are recommended in addition to a clinical exam every 6-12 months
For women without a known genetic predisposition but with a strong family history of breast cancer, annual mammography, annual MR, and annual or semiannual clinical exam should begin 10 years prior to the youngest age of breast cancer diagnosis in the family.
While breast self-exam has not been shown to affect breast cancer-related mortality, women are encouraged to be familiar with their bodies and to have any changes evaluated.
Ultrasound guided core
MR guided core
Atypical Ductal Hyperplasia (ADH)
Atypical Lobular Hyperplasia (ALH)
Flat Epithelial Atypia
Other Lesions with Atypia
Rationale for Surgical Excision
Importance of Concordance
Considerations for Avoiding Excision of Atypia on Core Needle Biopsy
Long-Term Risk of Breast Cancer Risk Associated With Atypical Hyperplasia