medwireNews: Survival among women participating in the POSH study who developed invasive breast cancer by the age of 40 years was comparable among patients with and without BRCA1 or BRCA2 mutations.
“Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences”, Diana Eccles, from the University of Southampton in the UK, and co-investigators therefore recommend in The Lancet Oncology.
The POSH (Prospective Outcomes in Sporadic versus Hereditary) study included 2733 patients who were given a diagnosis of young-onset invasive breast cancer of any histological subtype or stage at one of 127 UK hospitals between 2000 and 2008.
After a median of 8.2 years of follow-up, 678 patients had died and the majority (96%) of deaths were attributed to breast cancer, the researchers say.
The 2-year overall survival (OS) rate was 97.0% for the 12.4% of patients who tested positive for a BRCA1 or BRCA2 mutation; this did not significantly differ from the 96.6% rate for the remaining BRCA-negative patients. The corresponding 5- and 10-year OS rates were 83.8% versus 85.0%, and 73.4% versus 70.1%, and these again were comparable.
Moreover, OS did not significantly differ between the BRCA-positive and negative groups after adjusting for body mass index, ethnicity, tumour characteristics and receipt of taxane chemotherapy.
Subgroup analysis of the 558 patients with triple-negative breast cancer did suggest, however, that women with a BRCA mutation had significantly better OS at 2 years than those without, at 95% versus 91% and a hazard ratio of 0.59.
And post-hoc analysis confirmed that this survival advantage at 2 years existed when 31 patients who underwent bilateral mastectomy within a year of diagnosis were no longer included.
But the OS difference between triple-negative BRCA carriers and noncarriers no longer reached statistical significance after 5 and 10 years of follow-up, even when excluding bilateral mastectomy patients and those who were diagnosed with a new primary breast or ovarian cancer.
“[A]nalysis of early outcome data from trials exploring BRCA-deficient tumour treatment in patients with triple-negative breast cancer should be interpreted with caution in view of the possible early survival advantage for BRCA mutation carriers”, Diana Eccles and team warn.
Peter Fasching, from University Hospital Erlangen in Germany, writes in a linked comment that the POSH results “deliver a rationale for prospective studies” investigating whether bilateral mastectomy offers a survival benefit for women with BRCA1 or BRCA2 mutations.
Describing the report as “only the beginning of a better understanding of young patients with breast cancer”, he suggests: “The interaction between pregnancies at a young age, other genetic causes such as predisposition genes, and associated pathways such as RANK/RANKL are just some topics which could be addressed after the POSH study.”
Copson ER, Maisham TC, Tapper WJ, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol; Advance online publication 11 January 2018. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30891-4
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