Almost all breast malignancies are adenocarcinomas (>95%). In the most clinically useful classification system, breast cancers are divided based on the expression of hormone receptors—estrogen receptor (ER) and progesterone receptor (PR)—and the expression of the human epidermal growth factor receptor 2 (HER2, also known as ERBB2), into three major groups:
ER positive (HER2 negative; 50%–65% of cancers)
HER2 positive (ER positive or negative; 10%–20% of cancers)
Triple negative (ER, PR, and HER2 negative; 10%–20% of cancers)
These three groups show striking differences in patient characteristics, pathologic features, treatment response, metastatic patterns, time to relapse, and outcome ( 19.7
Fig. 19.26 ). Within each group are additional histologic subtypes (discussed later), some of which also have clinical importance.
Table19.7SummaryoftheMajorBiologicTypesofBreastCancer
Estrogen receptor positive, HER2-negative Estrogen receptor negative, HER2-negative HER2-positive
Fig.19.26Ageandtheincidenceofbreastcancersubtypes.
An alternative classification system with substantial overlap relies on gene expression profiling. This system, which is currently used mainly in the context of clinical research, divides breast cancers into four major types:
Luminal A. The majority are lower-grade ER-positive cancers that are HER2 negative
Luminal B. The majority are higher-grade ER-positive cancers that may be HER2 positive
HER2-enriched. The majority overexpress HER2 and do not express ER
Basal-like. The majority by gene expression profiling resemble basally located myoepithelial cells and are ER-negative, HER2-negative
Breast cancer rate (per 100,000 women)
HER2Positive(ERPositiveTripleNegative(ER,PR,FeatureERPositive/HER2NegativeorNegative)andHER2Negative)
CompleteresponsetoLowgrade(<10%),highergradeERpositive(15%),ERnegative30%chemotherapy(10%)(>30%)
MetastaticsitesBone(70%),viscera(25%),brainBone(70%),viscera(45%),brainBone(40%),viscera(35%),brain(<10%)(30%)(25%)
SimilargroupdefinedbymRNALuminalA(lowgrade),luminalBLuminalB(ERpositive),HER2-Basal-likeprofiling(highgrade)enriched(ERnegative)
CommonspecialhistologictypesLobular,tubular,mucinous,papillaryApocrine,micropapillaryCarcinomawithmedullaryfeatures
CommonsomaticmutationsPIK3CA (40%),TP53 (26%)TP53 (75%),PIK3CA (40%)TP53 (85%)
PIK3CA encodesphosphoinositide3-kinase(PI3K).
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A large number of risk factors for breast cancer have been identified (
Table 19.6 ). Some of the more important risk factors are summarized next.
Age and Gender. Breast cancer is rare in women younger than age 25, but increases in incidence rapidly after age 30 (
Fig. 19.26 ); 75% of women with breast cancer are older than 50 years of age, and only 5% are younger than 40. The incidence in men is only 1% of that in women.