At the present time, and while there is no specific evidence related to PALB2 mutation carriers, these guidelines are based on those that apply to management of breast cancer risk in BRCA2 mutation carriers.
There may be poorer breast cancer survival in women with PALB2 mutations compared to women with sporadic cancers (based on 116 Polish patients with one of 2 founder mutations PALB2 mutationsr and 29 Finnish women with PALB2 mutationsr).
Bilateral risk reducing mastectomy reduces cancer risk by at least 90% (depending on the operation performed) in BRCA mutation carriers.
Risk reducing salpingo-oophorectomy (RRSO) reduces breast cancer risk by 53% in BRCA2 carriers. Maximal breast cancer risk reduction achieved by RRSO is predicted when surgery occurs by age 40 years or whilst premenopausal. It should be noted, however, that germline mutations in PALB2 have not been associated with a high risk of ovarian cancer. Although no specific studies have been done, a similar breast cancer risk-reduction would be expected from RRSO for women with a loss-of-function PALB2 mutation.
MRI+mammogram (MMG) is the preferred screening technique due to its high sensitivity. MRI detects tumours which are smaller and more likely to be node-negative than mammography. MRI has a recall rate (requiring further investigation and/or biopsy) of 15% for initial screening, which decreases with subsequent rounds of screening to <10%.
There is no evidence to date that early detection of breast cancer is associated with a better prognosis and survival in BRCA1/2 or PALB2 mutation carriers. However, for women who do not chose risk reducing surgery, surveillance is strongly recommended.
Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high risk women. To date studies have not included enough BRCA1 or BRCA2 (or PALB2) mutation carriers to determine if it is effective for primary prevention in this population. Tamoxifen use is associated with a reduction in contralateral breast cancer risk by >67% in BRCA2 mutation carriers; such benefit is stronger if ovaries are still intact. Similar benefit might be expected in PALB2 mutation carriers. In view of the potential side effects associated with tamoxifen/raloxifene, risk-reducing medications should be discussed with an experienced medical professional to determine the relevant risks and benefits in an individual mutation carrier. See Cancer Australia Risk-reducing medication resource.
There is currently no effective surveillance that detects early pancreatic cancer.