Page 543 - Concise Pathology for Exam Preparation ( PDFDrive )

528 SECTION II Diseases of Organ Systems

• Genetic factors:
• Mutations in BRCA1 (familial breast and ovarian cancer), BRCA2 (familial breast and
ovarian cancer), p53 (Li-Fraumeni syndrome) and CHEK2 (responsible for 1% of all
breast cancers).
• Family history of breast cancer (affected first-degree relatives who do not carry an
established breast cancer gene mutation).
• Overexpression of HER2/neu proto-oncogene.
• Amplification of RAS and MYC genes.
• Breastfeeding: The longer the duration of breastfeeding, the less the incidence of breast
carcinoma.
• Hormonal influences: Oestrogen excess (long duration of reproductive life, nulliparity,
first child at a late age, increasing age and exogenous oestrogens). Oral contraceptives
are not known to be associated with an increased incidence. Oophorectomy decreases
the risk by decreasing endogenous oestrogens. Also, drugs like tamoxifen (blocks oes-
trogen) and aromatase inhibitors (decrease oestrogen synthesis) decrease the risk of
ER-positive cancers.
• Environmental factors: Radiation exposure, organochlorine pesticides (have oestro-
gen-like effects) and alcohol intake.
• Proliferative breast disease/carcinoma of contralateral breast or endometrium
(have several common risk factors).
• Breast density: High breast density on mammography has a 4–5 times higher risk of
ER-positive and ER-negative cancers.
• Obesity: Obese women less than 40 years have anovulatory cycles and lower progester-
one levels thereby reducing the risk, whereas, postmenopausal obesity increases the risk
attributed to oestrogen synthesis in the fat depots.
Familial breast cancer: Many familial cancers and 80–90% of single gene familial breast
cancers are due to two autosomal dominant genes: BRCA1 and BRCA2 (Table 19.1).

TABLE 19.1. Differences between BRCA1- and BRCA2-associated breast cancers
BRCA2
Features BRCA1 Chromosome
17q21 13q12.3 Smaller
Gene size
Larger • Tumour suppression • Tumour suppression
Functions • Transcription regulation • Transcription regulation
• DNA repair • DNA repair
Age at onset Younger (40–50 years) 50 years
Risk of other tumours Carcinoma of ovary (more than BRCA2), Carcinoma of ovary, prostate, pancreas,
prostate, pancreas, fallopian tube and stomach, melanoma, biliary system,
male breast cancer (less than BRCA1). pharynx and male breast cancer
Pathology of breast cancers Greater incidence of medullary carcinoma, Similar to sporadic cancers (ER-nega-
poorly differentiated carcinoma, ER-PR tive cancers)
and HER2/neu-negative carcinoma and
carcinoma with P53 mutations

Sporadic breast cancer: The main risk factors for sporadic cases of carcinoma breast in-
clude oestrogen excess, reproductive history, gender and age.

Distribution of Carcinoma Breast
Central area (20%), upper outer quadrant (50%), upper inner quadrant (10%), lower
outer quadrant (10%) and lower inner quadrant (10%). Left breast is more often involved
than right.

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