Cancer Screening In Survivors Research Articles

Prevalence of unexpected actionable germline pathogenic variants identified on broad-based multi-gene panel testing in a cohort of cancer patients.

10523 Background: Broad-based germline multi-gene panel testing (MGPT) for inherited predisposition has become increasingly common for cancer patients. Both indications for germline testing and the spectrum of genes on MGPT have expanded. We sought to examine the frequency of an unexpected pathogenic/likely pathogenic variant (P/LPV) in patients with a variety of solid and hematologic malignancies undergoing MGPT. Methods: A retrospective review of patients with a history of cancer who underwent MGPT at a single institution from 2015 to 2021 with MGPT of > 20 cancer predisposition genes. Low penetrance genes and genes with a recessive inheritance pattern were excluded. Deidentified pedigrees were analyzed by genetic counselors for clinical diagnostic criteria and gene-specific national testing guidelines to determine whether clinical suspicion of the P/LPV was present. Results: 10,975 cancer patients underwent MGPT. 1,180 (10.9%) patients were found to have > 1 P/LPV in a moderate or highly penetrant cancer susceptibility gene. 357 (3.3%) of the P/LPV were unexpected based on patient’s personal cancer history alone. 208 (1.9%) of the P/LPV remained unexpected after patient and family cancer histories were considered. Most common cancer subtypes with an unexpected P/LPV were breast [1.5% (83/5691)], prostate [2.1% (28/1300)], colorectal [2.2% (18/823)], ovarian/fallopian [1.7% (13/781)] and uterine [ 2.8% (10/352)] cancer. Most frequent unexpected P/LPV were PMS2 (n = 19), MITF (n = 18), ATM (n = 18), BRIP1 (n = 17), CHEK2 (n = 14), HOXB13 (n = 13), SDHA (n = 12), BRCA2 (n = 7), MSH6 (n = 7), SDHC (n = 7), TP53 (n = 7), and PALB2 (n = 6). No predictor of having an unexpected P/LPV was identified in multivariable logistic regression analysis. Low penetrance or recessive variants were found in 521 (4.8%) patients. Variants of uncertain significance (VUS) were found in 3,774 (35.0%) patients. Conclusions: This large retrospective analysis of cancer patients undergoing MGPT identified an overall rate of 1.9% of P/LPV in actionable cancer predisposition genes. Findings were more often unexpected (3.3%) when considering only the patient cancer history, endorsing the importance of family cancer history for consideration of more targeted genetic testing. Identification of moderate or highly penetrant P/LPV in cancer patients is increasingly important in guiding treatment decisions, cancer screening in survivors and testing of at-risk family members. These findings may justify consideration of broader MGPT panels especially when family cancer history is uncertain or unavailable. MGPT also detected a high rate of VUS, reinforcing the importance of physician education to ensure appropriate interpretation and management.

Invited Commentary: Hodgkin Lymphoma and Beyond: Breast Cancer Screening in Survivors of Childhood Cancer

HomeRadioGraphicsVol. 43, No. 4 PreviousNext Breast ImagingInvited Commentary: Hodgkin Lymphoma and Beyond: Breast Cancer Screening in Survivors of Childhood CancerSona A. Chikarmane Sona A. Chikarmane Author AffiliationsFrom the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115.Address correspondence to the author (email: [email protected]).Sona A. Chikarmane Published Online:Mar 16 2023https://doi.org/10.1148/rg.220203MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In

Breast Cancer Screening in Survivors of Childhood Cancer

Women who survived childhood cancers or cancers at a young age are at high risk for breast cancer later in life. The accentuated risk is notable among those treated at a young age with a high radiation dose but also extends to survivors treated with therapies other than or in addition to radiation therapy. The predisposing risk factors are complex. Advances in radiation therapy continue to curtail exposure, yet the risk of a second cancer has no dose threshold and a long latency period, and concurrent use of chemotherapy may have an additive effect on long-term risk of cancer. Early screening with annual mammography and MRI is recommended for chest radiation exposure of 10 Gy or greater, beginning 8 years after treatment or at age 25 years, whichever is later. However, there is a lack of recommendations for those at high risk without a history of radiation therapy. Because mortality after breast cancer among survivors is higher than in women with de novo breast cancer, and because there is a higher incidence of a second asynchronous breast cancer in survivors than that in the general population, regular screening is essential and is expected to improve mortality. However, awareness and continuity of care may be lacking in these young patients and is reflected in their poor screening attendance. The transition of care from childhood to adulthood for survivors requires age-targeted and lifelong strategies of education and risk prevention that are needed to improve long-term outcomes for these patients. © RSNA, 2023 See the invited commentary by Chikarmane in this issue. Quiz questions for this article are available through the Online Learning Center.

Expectations for survivorship care among hematology oncology and primary care providers.

5 Background: Significant controversy exists between hem/onc & primary care providers regarding various aspects of survivorship care. Here we administer a 23 question survey to address these discrepancies. Methods: A 23 question (Q) electronic survey was created on www.surveymonkey.com and sent to providers at Cancer Treatment Centers of America, & The University of Miami Health Network. Survey included provider demographics (7Qs) and practice preference Qs (16Qs). Survey asked: who should be primary responsible for managing cardiotoxicity (CT), cardiovascular risk reduction (CRD), physical activity assessments (PA), nutrition (N), weight (W), anxiety depression panic disorder PTSD (ADPP), cognitive function (CF), fatigue (F), sexual function (SF), lymphedema (L), side effect of hormonal agents (SEH), side effect of targeted agents (SET), side effect of bone modifying agents (SEB), vaccinations (V), cancer screening (CS), sleep disorders (SD)? Answer choices were 1) Hematologist Oncologist (HO), 2) Primary Care Provider (PCP), 3) Both HO + PCP (BO), 4) Other (O). Results: 55 providers enrolled in the survey (92% physician 6% ARNP 2% other). 56% hem/onc, 7% PCP, 37% subspecialty. 56% hospital based, 20% academic, 16% multispecialty practice, 8% other. Survey results: (CT): HO 29%, PCP 5%, BO 60%, 0 6%, (CRD): HO 7%, PCP 49%, BO 36%, 8% O, (PA): HO 5%, PCP 45%, BO 38%, O 12%, (N): HO 5%, PCP 38%, BO 35%, O 12%, (W): 4%, PCP 47%, BO 31%, O 16%, (ADPP): HO 5%, PCP 33%, BO 38%, O 24%, (CF): HO 5%, PCP 33%, BO 45%, O 17%, (F): HO 4%, PCP 36%, BO 53%, O 7%, (SF): HO 5%, PCP 22%, BO 49%, O 24%, (L): HO 31%, PCP 7%, BO 36%, O 26%, (SEH): HO 62%, PCP 4%, BO 27%, O 7%, (SET): HO 69%, PCP 4%, BO 20%, O 7%, (SEB): HO 62%, PCP 4%, PCP 25%, O 9%, (V): HO 16%, PCP 42%, BO 36%, O 6%, (CS): HO 9%, PCP 38%, BO 47% O 6%, (SD): 3% HO, PCP 51%, BO 31%, O 15%. Conclusions: In our study we found that the majority of providers think PCPs should manage: CRD & SD; HO should manage: SEH, SET, SEB; BO should manage: CT, F. A minority of providers favored combined approach (BO) for: CRD, ADPP, CF, SD, L, CS in survivors.

Screening Childhood Cancer Survivors for Breast Cancer

The development of second primary solid tumors, especially breast neoplasms, is increased among patients who have survived childhood or adolescent malignancies. With the increased long-term survival of patients with pediatric cancer, questions regarding breast cancer screening in this group have been raised. At this time, there are no established guidelines for breast cancer surveillance in this high-risk population. The objective of this review is to summarize the incidence, list additional risk factors for the development of breast cancer, and discuss the benefits of early detection of second primary breast cancers in pediatric cancer survivors. We have devised an algorithm for breast cancer screening in survivors of childhood malignancy. Implications of treatment with radiation and chemotherapy and the influence on prognosis of genetic abnormalities such as p53 mutations are debated.