From the Journals

Inherited mutations drive 12% of Nigerian breast cancer

Key clinical point: Loss-of-function mutations in four breast cancer risk genes account for much of the disease among Nigerian women with the disease.

Major finding: Inherited mutations of the BRCA1, BRCA2, PALB2, or TP53 gene account for 12% of breast cancer in Nigerian women.

Study details: The Nigerian Breast Cancer Study comprised 1,136 women with invasive breast cancer and 997 controls.

Disclosures: Dr. Olopade had no financial disclosures. The study was largely funded by the National Institutes of Health and the Susan G Komen Foundation.

Source: Olopade et al. J Clin Oncol. 2018 Aug 21. doi: 10.1200/JCO.2018.78.3977.

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Large-scale genetic screening would be challenging in Nigeria – and in any country

The findings of the Nigerian Breast Cancer Study make a case for large-scale breast cancer gene screening. But even in a wealthy country with good infrastructure, such a program would be dauntingly complex, Ophira Ginsburg, MD, and Paul Brennan, PhD, wrote in an accompanying editorial.

“Given the estimated 40,983 women in Nigeria younger than age 65 years who will be newly diagnosed with breast cancer in 2030, the estimated mutation carrier frequency for a high-risk gene of 11%-12% translates to approximately 5,000 women with breast cancer each year who might benefit directly from tailored risk-reducing strategies. Moreover, 50% of these women’s sisters and daughters would also stand to benefit,” they wrote.

However, 32 million women would need to be screened to find the 220,000 with one of the mutations – a task that is “clearly beyond the scope of most countries.

“Furthermore, women with pathogenic variants would require intensive follow-up and intervention strategies to reduce their risk of developing breast, ovarian/fallopian tube, and potentially other cancers depending on the gene involved. Importantly, this approach would not address the larger problem of the high breast cancer mortality among the vast majority of women without a pathogenic variant but who make up approximately 85% of the breast cancer burden.”

The World Health Organization recognizes this challenge; the agency doesn’t even recommend mammogram-based population screening unless there is a basic, reliable infrastructure including electricity, quality-assurance measures, referral and recall mechanisms, and monitoring and evaluation frameworks. But WHO does suggest some core elements to guide a country’s comprehensive cancer management strategy, including:

• Considering the whole continuum from prevention to palliation.

• Providing a sustainable strategic plan on the basis of the country’s cancer burden, risk factor prevalence, and the resources available to implement the plan.

• Developing an evidence-based approach generated by population-based cancer registries.

“As many countries improve their cancer systems, investing in human resources, infrastructure, monitoring, and evaluation, it is timely to consider how to evaluate readiness to undertake a population-level cancer genetics intervention and consider the core elements that should be in place to make a substantive effect on cancer mortality.”

Dr. Ginsburg is with the Perlmutter Cancer Center of New York University. Dr. Brennan is with the International Agency for Research on Cancer, Lyon, France.



About one in eight Nigerian women with breast cancer has an inherited mutation of the BRCA1, BRCA2, PALB2, or TP53 gene.

A new analysis of the Nigerian Breast Cancer Study confirmed that these inherited mutations drive about 12% of the country’s breast cancer cases. The findings could pave the way for the first large-scale national breast cancer gene screening program, wrote Olufunmilayo I. Olopade, MD, and her colleagues. The report is in the Journal of Clinical Oncology.

“We suggest that genomic sequencing to identify women at extremely high risk of breast cancer could be a highly innovative approach to tailored risk management and life-saving interventions,” wrote Dr. Olopade, director of the Center for Clinical Cancer Genetics at the University of Chicago, and her colleagues. “Nigeria now has data to prioritize the integration of genetic testing into its cancer control plan. Women with an extremely high risk of breast cancer because of mutations in these genes can be identified inexpensively and unambiguously and offered interventions to reduce cancer risk.”

And, since about half of the sisters and daughters of affected women will carry the same mutation, such a screening program could reach far beyond every index patient identified, the investigators noted.

“If these women at very high risk can be identified either through their relatives with breast cancer or in the general population, resources can be focused particularly on their behalf. For as-yet unaffected women at high genetic risk, these resources would be intensive surveillance for early detection of breast cancer and, after childbearing is completed, the possibility of preventive salpingo-oophorectomy. Integrated population screening for cancer for all women is the goal, but focused outreach to women at extremely high risk represents an especially efficient use of resources and an attainable evidence-based global health approach.”

The Nigerian Breast Cancer Study enrolled 1,136 women with invasive breast cancer from 1998 to 2014. These were compared with 997 women without cancer, matched from the same communities. Genetic sequencing searched for mutations in both known and breast cancer genes.

Cases and controls were a mean of 47 years old; only 6% of cases reported a family history of breast cancer. Of 577 patients with information on tumor stage, 86% (497) were diagnosed at stage III (241) or IV (256).

Among the cases, 167 (14.7%) carried a mutation in a breast cancer risk gene, compared with 1.8% of controls. BRCA1 was the most common mutation, occurring in 7% of patients; these women were 23 times more likely to develop breast cancer than were those without the gene (odds ratio, 23.4). BRCA2 was the next most common, occurring in 4% of cases and conferring a nearly 11-fold increased risk (OR, 10.76). PALB2 occurred in 11 cases (1%) and no controls, and TP53 in four cases (0.4%).

Women with the BRCA1 mutation were diagnosed at a significantly younger age than were other patients (42.6 vs. 47.9 years), as were carriers of the TP53 mutation (32.8 vs. 47.6 years).

Ten other genes (ATM, BARD1, BRIP1, CHEK1, CHEK2, GEN1, NBN, RAD51C, RAD51D, and XRCC2) carried a mutation in at least one patient each. “When limited to mutations in the four high-risk genes, 11%-12% of cases in this study carried a loss-of-function variant.”

Dr. Olopade had no financial disclosures.

SOURCE: Olopade et al. J Clin Oncol. 2018 Aug 21. doi: 10.1200/JCO.2018.78.3977.

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