At the present time, and while there is no specific evidence related to PALB2 pathogenic variant carriers, these guidelines are inferred from those recommended for management of breast cancer risk in BRCA2 pathogenic variant carriers, and take into account the knowledge that the cancer risk in some PALB2 pathogenic variant families is lower than the usual threshold for recommending risk-reducing surgery or screening from age 30 years.
The majority of PALB2-associated breast cancers are ER+.r There may be poorer breast cancer survival in women with PALB2 pathogenic variants compared to women with sporadic cancers (based on 116 Polish patients with one of 2 founder PALB2 pathogenic variantsr and 29 Finnish women with PALB2 pathogenic variantsr).
Bilateral risk-reducing mastectomy reduces cancer risk by at least 90% (depending on the operation performed) in BRCA1 or BRCA2 pathogenic variant carriers.rr
MRI is the preferred screening technique due to its high sensitivity compared with mammogram (MMG) or ultrasound (US). The addition of MMG is limited, and does not lead to a significant increase in sensitivity compared with MRI alone.r There is no added value of ultrasound in women undergoing MRI for screening. MRI detects tumours which are smaller and more likely to be node-negative than MMG. 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, BRCA2 or PALB2 pathogenic variant carriers. However, for women who do not choose 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) pathogenic variant 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 in BRCA1 and BRCA2 pathogenic variant carriers with breast cancer; such benefit is stronger if ovaries are still intact.r Similar benefit might be expected in PALB2 pathogenic variant 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 pathogenic variant carrier. See COSA - Medications to lower the risk of breast cancer: clinician guide.
Breast cancer (male)
No trials have evaluated whether manual palpation is effective but mammography not useful. Other factors such as obesity, chest wall radiation and gynaecomastia can increase the risk of male breast cancer.r
Although there are no specific RRSO studies to date including PALB2 pathogenic variants, evidence suggests that ≥4% lifetime risk of ovarian cancer warrants consideration of RRSO in premenopausal women on the basis of family history of ovarian cancer.r The recommendation for surgery is generally after age 50 years.
There is currently no effective surveillance that detects early pancreatic cancer.