History and exam

Key diagnostic factors

common

presence of risk factors

Key factors include family history of breast cancer, benign breast disease on prior biopsy or hereditary syndromes such as Li-Fraumeni syndrome, Cowden syndrome, or hereditary breast ovarian cancer syndrome.

family history of breast cancer

In a large population-based prospective cohort (UK Biobank), a positive family history of breast cancer was associated with an increased risk for ductal carcinoma in situ (DCIS) among premenopausal women (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.00 to 1.98) and postmenopausal women (HR 1.51, 95% CI 1.25 to 1.84).[70]

Family history increases risk for lobular carcinoma in situ (LCIS) 1.7-fold.[20]

Some genetically defined syndromes increase risk of multiple cancers. One example is breast cancer: BRCA-related genes 1 and 2 (cancers of breast, fallopian tube, prostate, and ovary).[23] Another is Li-Fraumeni syndrome (breast cancer, osteosarcoma, and soft-tissue sarcomas).

Other diagnostic factors

common

nipple discharge

Unilateral discharge, whether bloody or not, may indicate a benign tumour such as a papilloma, or less commonly ductal carcinoma in situ or invasive breast cancer.

The first symptom in males diagnosed with DCIS is generally bloody nipple discharge.[46]

uncommon

breast lump

Can be smooth or nodular.

eczema-like rash on nipple

Bleeding from or excoriation of the nipple are typical presenting signs of Paget's disease of the breast.

ulceration

Breast cancer that is ignored can present as an ulcerating skin lesion.

Risk factors

strong

family history of breast cancer

Increases risk for ductal carcinoma in situ (DCIS) 1.5-fold and for lobular carcinoma in situ (LCIS) 1.7-fold.[20]

May increase risk of DCIS because of genetic factors, shared exposures to other risk factors, or because women with a positive family history are more likely to have regular mammography.

Because DCIS is most often first detected mammographically, mammography frequency often confounds studies of DCIS incidence.[21]

benign breast disease on prior biopsy

Increases risk for ductal carcinoma in situ up to 3.5-fold and for lobular carcinoma in situ up to 4.2-fold.[20]

hereditary breast ovarian cancer syndrome

Approximately 85% of hereditary breast and ovarian cancers are caused by mutations in BRCA1 or BRCA2 genes.[22]

In one prospective cohort study, the cumulative risk of breast cancer up to age 80 years was found to be similar for BRCA1 carriers (72%, 95% confidence interval [CI] 65% to 79%) and BRCA2 carriers (69%, 95% CI 61% to 77%). However, up to age 50 years, the cumulative risk was found to be higher for BRCA1 carriers.[23]

Li-Fraumeni syndrome

Li-Fraumeni syndrome is caused by mutations in the TP53 gene; it is characterised by early-onset (<40 years old) breast cancer, soft-tissue sarcomas, leukaemia, primary brain tumours, and adrenocortical carcinomas. Among patients with Li-Fraumeni syndrome, up to one third of the cancers are of breast origin.[24]

Cowden syndrome

Cowden syndrome is caused by mutations in the PTEN gene.

Approximately 75% of women with the syndrome have benign breast disease and 25% to 50% will develop breast cancer.[25]

hereditary diffuse gastric cancer (HDGC)

HDGC is caused by germline mutations in the CDH1 (E-cadherin) gene and predisposes an individual to breast and colorectal cancer.[26] In one study, the cumulative risk of breast cancer in women with CDH1 mutations was 39%. The breast tumours tend to be of the lobular subtype.[26]

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is caused by mutations in the STK11 gene and predisposes to cancers, particularly breast and gynaecological cancers.[27][28] One study reported a relative risk of 20.3 for breast and gynaecological cancer in women with Peutz-Jeghers.[29]

Klinefelter syndrome

There is an increased risk of breast cancer in males with Klinefelter syndrome.[30]

weak

older age at menopause

Increases the risk of both ductal carcinoma in situ and lobular carcinoma in situ[20]

older age at first full-term pregnancy

Age at first birth influences risk of ductal carcinoma in situ but not so clearly lobular carcinoma in situ.[20]

nulliparity

May be associated with an increased risk of ductal carcinoma in situ but not clearly lobular carcinoma in situ.[20]

low physical activity

Lifetime physical activity is associated with an approximately 35% lower risk of in situ carcinoma compared to women with an inactive lifestyle.[31]

high vitamin A intake

High vitamin A intake may be associated with increased risk of ductal carcinoma in situ but not lobular carcinoma in situ.[32]

ataxia telangiectasia

This autosomal-recessive condition, which results in cerebellar ataxia, immune defects, telangiectasias, radiosensitivity, and a predisposition to malignancy, is caused by mutations in the ATM gene.[33]

Study results vary regarding the influence of this mutation on breast cancer risk.[34]

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