Prognosis

The prognosis of patients with primary invasive breast cancer is dependent on many different factors, such as age, comorbidities, disease stage, and tumour biology.

In general, patients with a long disease-free interval between diagnosis and recurrence; hormone receptor-positive status; favourable response to initial treatment; limited lesions; small tumours; and HER2-negative status are likely to have improved survival outcomes than those with the opposite characteristic.

According to US data from the Surveillance, Epidemiology, and End Results (SEER) database (between 2014 and 2020), the 5-year relative survival rate for women with localised breast cancer is 99.6%.[8]

Men have higher mortality from breast cancer at 3 years, 5 years, and overall, compared with women. The association of male sex with higher mortality persists after adjustments for age, race/ethnicity, access to care, clinical characteristics, and treatment factors.[422]

There are several validated prognostic tools that can be used to predict recurrence and mortality in patients with breast cancer.

Tumour-based guides to determining prognosis

Gene expression assays may be used for prognostication and to guide decisions on adjuvant chemotherapy.[149][150][151][152][153]

Oncotype DX® is the preferred assay to guide adjuvant endocrine therapy and chemotherapy in patients with HR-positive, HER2-negative disease who are node-negative or post-menopausal with node-positive disease (1-3 positive nodes).[117][153]​​​​[154]

Pre-menopausal patients with 1-3 positive nodes benefit from chemotherapy regardless of genomic assay result. The clinical utility of assays in node-positive disease with ≥4 nodes is unknown.[153]

Other assays, such as Mammaprint®, Breast Cancer Index (BCI), Prosigna®, and EndoPredict®, may be used to provide prognostic information in post-menopausal women or women aged >50 years who are node negative. Mammaprint® and EndoPredict® may also be used for post-menopausal women or women aged >50 years with 1-3 positive nodes. However, the ability of these assays to predict therapeutic benefit is less certain.[117][153]

Other prognostic biomarkers

Carcinoembryonic antigen, programmed death-ligand 1 (PD-L1) expression, circulating tumour cells, stromal tumour-infiltrating lymphocytes, and BRCA1 gene promoter methylation have been studied regarding their prognostic/predictive significance.

PD-L1 expression on tumour cells is associated with shorter disease-free survival and overall survival.[423]

Increased circulating tumour cell count before neoadjuvant chemotherapy is associated with poorer overall survival, disease-free survival, and locoregional relapse-free interval.[424]

Quantity of stromal tumour-infiltrating lymphocytes is significantly associated with disease-free and overall survival in women with early triple-negative breast cancer treated with adjuvant anthracycline chemotherapy.[425]

Increased stromal tumour-infiltrating lymphocytes in the primary tumour are associated with decreased risk of ipsilateral breast tumour recurrence.[426]

Methylation of the BRCA1 gene promoter is associated with poor overall survival and poor disease-free survival.[427]

Consideration for comorbidities

Comorbidities exert a significant negative influence on patient outcome. This effect was shown in a retrospective analysis of 936 women, aged 40-84 years, whose tumour and treatment history was obtained from the Metropolitan Detroit Cancer Surveillance System.[428] All-cause mortality in patients who had ≥3 selected comorbid conditions was 4 times higher than that in patients who had no comorbid conditions. This effect was unaffected by age, disease stage, tumour size, histological type, type of treatment, race, and social and behavioural factors.

Data from the Eindhoven Cancer Registry demonstrated that while patients with serious comorbidities had comparable treatment plans and complications, their overall survival was poorer.[429]

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