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]National Cancer Institute. Cancer stat facts: female breast cancer [internet publication].
https://seer.cancer.gov/statfacts/html/breast.html
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]Wang F, Shu X, Meszoely I, et al. Overall mortality after diagnosis of breast cancer in men vs women. JAMA Oncol. 2019 Sep 19;5(11):1589-96.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2751525
http://www.ncbi.nlm.nih.gov/pubmed/31536134?tool=bestpractice.com
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]Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015 Nov 19;373(21):2005-14.
https://www.nejm.org/doi/full/10.1056/NEJMoa1510764
http://www.ncbi.nlm.nih.gov/pubmed/26412349?tool=bestpractice.com
[150]Goncalves R, Bose R. Using multigene tests to select treatment for early-stage breast cancer. J Natl Compr Canc Netw. 2013 Feb 1;11(2):174-82.
https://www.jnccn.org/content/11/2/174.long
http://www.ncbi.nlm.nih.gov/pubmed/23411384?tool=bestpractice.com
[151]Harbeck N, Sotlar K, Wuerstlein R, et al. Molecular and protein markers for clinical decision making in breast cancer: today and tomorrow. Cancer Treat Rev. 2014 Apr;40(3):434-44.
http://www.ncbi.nlm.nih.gov/pubmed/24138841?tool=bestpractice.com
[152]Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med. 2019 Jun 20;380(25):2395-405.
https://www.nejm.org/doi/10.1056/NEJMoa1904819
http://www.ncbi.nlm.nih.gov/pubmed/31157962?tool=bestpractice.com
[153]Andre F, Ismaila N, Allison KH, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2022 Jun 1;40(16):1816-37.
https://ascopubs.org/doi/10.1200/JCO.22.00069
http://www.ncbi.nlm.nih.gov/pubmed/35439025?tool=bestpractice.com
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]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[153]Andre F, Ismaila N, Allison KH, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2022 Jun 1;40(16):1816-37.
https://ascopubs.org/doi/10.1200/JCO.22.00069
http://www.ncbi.nlm.nih.gov/pubmed/35439025?tool=bestpractice.com
[154]National Institute for Health and Care Excellence. Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. Dec 2018 [internet publication]
https://www.nice.org.uk/guidance/dg34
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]Andre F, Ismaila N, Allison KH, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2022 Jun 1;40(16):1816-37.
https://ascopubs.org/doi/10.1200/JCO.22.00069
http://www.ncbi.nlm.nih.gov/pubmed/35439025?tool=bestpractice.com
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]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[153]Andre F, Ismaila N, Allison KH, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2022 Jun 1;40(16):1816-37.
https://ascopubs.org/doi/10.1200/JCO.22.00069
http://www.ncbi.nlm.nih.gov/pubmed/35439025?tool=bestpractice.com
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]Huang W, Ran R, Shao B, et al. Prognostic and clinicopathological value of PD-L1 expression in primary breast cancer: a meta-analysis. Breast Cancer Res Treat. 2019 Nov;178(1):17-33.
http://www.ncbi.nlm.nih.gov/pubmed/31359214?tool=bestpractice.com
Increased circulating tumour cell count before neoadjuvant chemotherapy is associated with poorer overall survival, disease-free survival, and locoregional relapse-free interval.[424]Bidard FC, Michiels S, Riethdorf S, et al. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst. 2018 Jun 1;110(6):560-7.
https://academic.oup.com/jnci/article/110/6/560/4969338
http://www.ncbi.nlm.nih.gov/pubmed/29659933?tool=bestpractice.com
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]Loi S, Drubay D, Adams S, et al. Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast eancers. J Clin Oncol. 2019 Mar 1;37(7):559-69.
https://ascopubs.org/doi/10.1200/JCO.18.01010
http://www.ncbi.nlm.nih.gov/pubmed/30650045?tool=bestpractice.com
Increased stromal tumour-infiltrating lymphocytes in the primary tumour are associated with decreased risk of ipsilateral breast tumour recurrence.[426]Kovács A, Stenmark Tullberg A, Werner Rönnerman E, et al. Effect of radiotherapy after breast-conserving surgery depending on the presence of tumor-infiltrating lymphocytes: a long-term follow-up of the SweBCG91RT randomized trial. J Clin Oncol. 2019 May 10;37(14):1179-87.
https://ascopubs.org/doi/10.1200/JCO.18.02157
http://www.ncbi.nlm.nih.gov/pubmed/30939091?tool=bestpractice.com
Methylation of the BRCA1 gene promoter is associated with poor overall survival and poor disease-free survival.[427]Li S, He Y, Li C, et al. The association between the methylation frequency of BRCA1/2 gene promoter and occurrence and prognosis of breast carcinoma: a meta-analysis. Medicine (Baltimore). 2020 Mar;99(10):e19345.
https://journals.lww.com/md-journal/Fulltext/2020/03060/The_association_between_the_methylation_frequency.29.aspx
http://www.ncbi.nlm.nih.gov/pubmed/32150073?tool=bestpractice.com
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]Satariano WA, Ragland DR. The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med. 1994 Jan 15;120(2):104-10.
http://www.ncbi.nlm.nih.gov/pubmed/8256968?tool=bestpractice.com
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]Louwman WJ, Janssen-Heijnen ML, Houterman S, et al. Less extensive treatment and inferior prognosis for breast cancer patient with comorbidity: a population-based study. Eur J Cancer. 2005 Mar;41(5):779-85.
http://www.ncbi.nlm.nih.gov/pubmed/15763655?tool=bestpractice.com