Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study

Abstract

SummaryBackgroundRetrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer.MethodsWe did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing.FindingsBetween Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0–9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5–98·4] vs 96·6% [95·8–97·3]; at 5 years: 83·8% [79·3–87·5] vs 85·0% [83·5–86·4]; at 10 years: 73·4% [67·4–78·5] vs 70·1% [67·7–72·3]; hazard ratio [HR] 0·96 [95% CI 0·76–1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89–97] vs 91% [88–94]; HR 0·59 [95% CI 0·35–0·99]; p=0·047) but not 5 years (81% [73–87] vs 74% [70–78]; HR 1·13 [0·70–1·84]; p=0·62) or 10 years (72% [62–80] vs 69% [63–74]; HR 2·12 [0·82–5·49]; p= 0·12).InterpretationPatients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. 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.FundingCancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.

Subtypes of Breast Cancer in Lao P.D.R.: A Study in a Limited-Resource Setting

“…Regarding the breast cancer subtype, the prevalence of hormone receptor-positive cases was 44.7%, which is much lower than the results found in other developed countries in Asia, Europe and the US: 71% in Japan (Shibuta et al, 2011), 62% in Taiwan (Lin et al, 2009), 72% in Europe (Blows et al, 2010), and 72.7% in the US (Howlader et al, 2014). Our patients presented at young ages, with a mean age of 48 years old, and they tended to have higher histologic grade, and this trend can be observed in a recent study (Copson et al, 2018). The mean age is high in other developed countries in Asia, such as Japan (56 years) and Taiwan (50 years).…”

My mind is made up: Cancer concern and women’s preferences for contralateral prophylactic mastectomy

“…In a recently published cohort study of outcomes in early‐onset breast cancer, Copson et al () concluded that decisions regarding risk reducing strategies, such as CPM, should not only take into account ongoing cancer risk but also patient preferences (Copson et al, ). Our results show that a majority of women have strongly held preferences; they favour routine monitoring when choosing how they would manage the ongoing risk of cancer recurrence.…”

Multifocal breast cancers are more prevalent in BRCA2 versus BRCA1 mutation carriers

“…The POSH (Prospective Outcomes in Sporadic versus Hereditary breast cancer) study recruited young women (aged 18–40) diagnosed with primary breast cancer in the United Kingdom between 2000 and 2008 . The study methodology (including genotyping methods) and outcomes have previously been reported . Data on tumour focality/centricity in the POSH study patients was obtained from medical records from participating centres.…”