PALB2 mutations and breast cancer risk

In their article in the NEJM Antoniou et al report the risk of breast cancer among 362 members of 154 families who had deleterious truncating, splice, or deletion mutations in PALB2.

The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% by 50 years of age and 35% by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort and by other familial factors. The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% for those with no family history of breast cancer to 58% for those with two or more first-degree relatives with breast cancer at 50 years of age.

The authors concluded loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer.

Ultrasound as an adjunct to mammography detects more cancers in women with dense breasts

Scheel et al study published in AJOG, reports on their review from 189 studies of screening for breast cancer in women with dense breasts.  From the total of 189 studies, 12 that were conducted between January 2000 and April 2013 met the criteria set by the researchers. The reporting of breast cancer risk factors varied across studies; however, the populations studied tended to be at greater than average risk for developing breast cancer.

Overall, ultrasound (US) detected an additional 0.3-7.7 cancers/1,000 examinations (Median 4.2) and was associated with an additional 11.7-106.6 biopsies/1,000 examinations (Median 52.2). They found that US screening for women with dense breast tissue increases cancer detection and leads to fewer false positive biopsies compared to mammography alone.

The researchers report that most of the additional cancers identified by ultrasound were small and node-negative stage. Such cancers can be curable and require less aggressive treatment because of the early detection. They suggest physicians should discuss the use of ultrasound as an adjunct to mammography with patients who have dense breast tissues.  They should explain the benefits and also potential to lead to additional percutaneous biopsies in easy to understand terms and arrive at a shared decision consistent with individual patient’s preferences and values.

The analysis of data from the reviewed studies suggest that potential benefits and harms could accrue if screening ultrasound is added to mammographic screening of women with dense breast tissue.

DOI: http://dx.doi.org/10.1016/j.ajog.2014.06.048

MRI and Mammography Combined are Effective in Detecting Breast Cancer in Women at High Risk

Chiarelli et al in their JCO article report on Ontario’s Breast Screening Program of women age 30 to 69 years at high risk for breast cancer with annual magnetic resonance imaging (MRI) and digital mammography.

The study cohort consisted of 2,359 women. The following criteria were used to determine eligibility: known BRCA1, BRCA2 mutation, or other gene predisposing to a markedly increased risk of breast cancer, untested first-degree relative of a gene mutation carrier, family history consistent with hereditary breast cancer syndrome and estimated personal lifetime breast cancer risk of 25% or higher, or radiation therapy to the chest before age 30 years.

Digital mammograms were performed with standard craniocaudal and mediolateral oblique projections.  The minimum MRI standards were 1.5 Tesla units, gadolinium injection (0.1 to 0.2 mmol/kg) and a dedicated breast coil. Both breasts were imaged in axial and sagittal planes.  Most of the eligible women (90.7%) had their MRI within a month from their mammograms.  Of the 2,359 eligible women 2,290 were screened.  Of the women screened 2,157 had an MRI and were included in the study as women who had only a mammogram were excluded.

The recall rate of 15% was significantly higher among women who had abnormal MRI alone compared with 6.4% when mammogram alone was used.  Of the 35 breast cancers detected (16.3 per 1,000), none were detected by mammography alone, while 23 (65.7%) were detected by MRI alone (10.7 per 1,000), and 25 (71%) were detected among women who were known gene mutation carriers (30.8 per 1,000). The positive predictive value of 12.4% for detection was highest when findings from mammogram and MRI were combined.  Overall, the cancer detection rate was significantly higher for invasive cancers (12.6 per 1,000) compared with DCIS (3.7 per 1,000). Cancer detection rates were higher among women age 50 years (23.3 per 1,000) compared with women younger than age 50 years (13.3 per 1,000) and significantly higher among those who were known gene mutation carriers (30.8 per 1,000) compared with those with a family history plus an estimated lifetime cancer risk of 25% (6.9 per 1,000).

The authors conclude that screening with annual MRI combined with mammography is effective and could be implemented into an organized breast screening program for women at high risk for breast cancer as mammograms alone failed to detect early breast cancers. 

An editorial by Dr. Wendie Berg with comments on this topic was published by the Journal of Clinical Oncology.