Study: Survival and mutation status in breast cancer patients under age 40

IN-DEPTH REVIEW OF RESEARCH

Study background:

POSH (Prospective Outcomes in Sporadic versus Hereditary) breast cancer is a large, prospective study that recruited female patients in 127 hospitals in the United Kingdom from 2000 to 2008. Patients were ages 18 to 40 when first diagnosed with invasive breast cancer. Long-term follow up is ongoing.

Nearly 90% of patients received chemotherapy. Half had breast-conserving surgery and half had a mastectomy. The researchers examined detailed clinical follow-up information, including date and site of disease recurrence, at 6 months, 12 months, and then annually.  

Researchers of this study wanted to know:

What was the overall survival, from initial diagnosis to death from any cause, in young, BRCA-positive women compared to young, BRCA-negative women. It also assessed distant disease-free survival or the time from initial diagnosis to first distant disease.

Population(s) looked at in the study:

Among the 2,733 patients in the POSH study:

• 338 (12%) carried a BRCA1 or BRCA2 mutation
• 558 women (20%) had triple-negative breast cancer (TNBC)
  • BRCA mutations were identified in 136 (24%) of TNBC patients

Study findings: 

At an average follow-up of 8.2 years, 678 (25%) of the patients had died. Among these patients, 651 (96%) of 678 deaths were due to breast cancer. Statistical analysis showed no significant difference throughout the study in overall survival (OS) among patients with BRCA-positive breast cancer compared with those with BRCA-negative disease. The 2-year OS rate was 97.0% vs 96.6%, the 5-year OS rate was 83.8% vs 85.0%, and the 10-year OS rate was 73.4% vs 70.1%, respectively.

Researchers also analyzed a specific subgroup: women with BRCA mutations who had triple-negative breast cancer. This group had an improved 2-year OS rate of 95% compared to 91% for BRCA-negative patients; however, this survival advantage was not observed at the 5-year or 10-year follow-up.

Limitations:

Since study participation was restricted to women age 40 or younger, these results may not translate to BRCA mutation carriers who are older when diagnosed. It’s also important to note that during the study recruitment period (between 2000 and 2008), BRCA testing and risk-reducing surgery were not routine for early-stage breast cancer. In addition, breast cancer treatment recommendations in the U.K. have also changed over the course of recruitment, which may have affected the survival rates. The study was conducted prior to availability of panel testing, so the number of participants with mutations outside of BRCA1 and BRCA2 is unknown. 

Media Coverage

After this study was published in Lancet Oncology last month, a number of related media articles began with sensationalized headlines, including “A Gene That ‘Causes Cancer’ Probably Doesn’t Increase Your Chances of Dying from Cancer” and “The ‘Deadly Breast Cancer Gene’ Is a Myth, Lancet Study Confirms.” Understandably, these headlines created quite a social media stir. FORCE covered the uproar in two recent Headline Hype blog posts. 

Conclusions:

Understanding survival outcomes in young BRCA carriers with breast cancer is important because these patients have increased risk of also developing ovarian cancer, contralateral (in the other breast) breast cancer, or a new primary cancer in the same breast. These risks determine treatment, and knowing that young BRCA1 or BRCA2 mutation carriers do not have different survival outcomes than non-carriers can help with patient decisions on treatment and risk reduction.

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Posted 02/15/18