Publications by authors named "Steven A Narod"

538 Publications

Adjuvant olaparib - should all patients with breast cancer have genetic testing?

Authors:
Steven A Narod

Nat Rev Clin Oncol 2021 Jul 19. Epub 2021 Jul 19.

Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.

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http://dx.doi.org/10.1038/s41571-021-00544-7DOI Listing
July 2021

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool.

Cancer 2021 Jun 2. Epub 2021 Jun 2.

Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

Background: The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation.

Methods: BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age. Exposures, including preventive surgery, hormone use, and lifestyle factors, were captured by questionnaire. Performance on each of the 5 subtasks was analyzed according to various exposures. Analysis of covariance was used to compare overall scores.

Results: In total, 880 women completed the online cognitive assessment. The average age of the participants was 54 years (range, 23-86 years). The mean overall test score was 54.4 (range, 0-93). The individual subtask scores declined with age at test completion (P < .0001) and increased with level of education (P ≤ .01). Women who underwent a preventive oophorectomy had a significantly higher overall score compared with women who did not undergo this surgery (55.5 vs 50.5; P = .01). Reconstructive breast surgery was also associated with a higher overall score (56.5 vs 52.3; P = .005). Chemotherapy and hormone-replacement therapy were not predictive of the overall score.

Conclusions: These findings are reassuring to high-risk women who undergo early surgical menopause for their cancer predisposition. Further studies are needed to evaluate cognitive function over time when memory deficits become more prevalent.
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http://dx.doi.org/10.1002/cncr.33654DOI Listing
June 2021

The risk of contralateral breast cancer: a SEER-based analysis.

Br J Cancer 2021 May 26. Epub 2021 May 26.

Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.

Background: We sought to estimate the annual risk and 25-year cumulative risk of contralateral breast cancer among women with stage 0-III unilateral breast cancer.

Methods: We identified 812,851 women with unilateral breast cancer diagnosed between 1990 and 2015 in the SEER database and followed them for contralateral breast cancer for up to 25 years. Women with a known bilateral mastectomy were excluded. We calculated the annual risk of contralateral breast cancer by age at diagnosis, by time since diagnosis and by current age. We compared risks by ductal carcinoma in situ (DCIS) versus invasive disease, by race and by oestrogen receptor (ER) status of the first cancer.

Results: There were 25,958 cases of contralateral invasive breast cancer diagnosed (3.2% of all patients). The annual risk of contralateral breast cancer over the 25-year follow-up period was 0.37% and the 25-year actuarial risk of contralateral invasive breast cancer was 9.9%. The annual risk varied to a small degree by age of diagnosis, by time elapsed since diagnosis and by current age. The 25-year actuarial risk was similar for DCIS and invasive breast cancer patients (10.1 versus 9.9%). The 25-year actuarial risk was higher for black women (12.7%) than for white women (9.7%) and was lower for women with ER-positive breast cancer (9.5%) than for women with ER-negative breast cancer (11.2%).

Conclusions: Women with unilateral breast cancer experience an annual risk of contralateral breast cancer ~0.4% per year, which persists over the 25-year follow-up period.
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http://dx.doi.org/10.1038/s41416-021-01417-7DOI Listing
May 2021

PALB2 mutations and prostate cancer risk and survival.

Br J Cancer 2021 May 18. Epub 2021 May 18.

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.

Background: The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers.

Methods: We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509_510delGA and c.172_175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers.

Results: A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006).

Conclusion: In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.
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http://dx.doi.org/10.1038/s41416-021-01410-0DOI Listing
May 2021

The Screen Project: Guided Direct-To-Consumer Genetic Testing for Breast Cancer Susceptibility in Canada.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Women's College Research Institute, Women's College Hospital, Toronto, ON M5S 1B2, Canada.

There is limited information of the outcomes of direct-to-consumer testing for BRCA1 and BRCA2 mutations. The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation status. Patients enrolled in the study from 2017 to 2019 and were followed for one year after the receipt of a genetic test result. Study subjects registered online and were sent a saliva sample kit, which was shipped to the reference laboratory. Pre-test genetic counselling and counselling for mutation-negative subjects was optional and at the individual's discretion. There were 1269 tested individuals between March 2017 and January 2019. A total of 1157 (93%) were women and 87 (7%) were men. Sixty-six percent had a first- or second-degree relative with breast or ovarian cancer. Of the 1269 tested individuals, 30 (2.4%) had a pathogenic mutation in BRCA1 or BRCA2 (20 women and 10 men). Seventy-five percent of the female mutation carriers underwent a bilateral mastectomy and/or salpingo-oophorectomy within a year of receiving a positive result. Genetic counselling was available at no cost to all participants but was requested by only 5% of the non-carriers. The study subjects expressed a high degree of satisfaction with the process.
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http://dx.doi.org/10.3390/cancers13081894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071125PMC
April 2021

Serum Selenium Level Predicts 10-Year Survival after Breast Cancer.

Nutrients 2021 Mar 16;13(3). Epub 2021 Mar 16.

Read-Gene S.A., 72-003 Grzepnica, Poland.

In a recent prospective study, we reported an association between a low serum selenium level and five-year survival among breast cancer patients. We now have updated the cohort to include 10-year survival rates. A blood sample was obtained from 538 women diagnosed with first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected before initiation of treatment. Serum selenium levels were quantified by mass spectroscopy. Each patient was assigned to one of four quartiles based on the distribution of serum selenium levels in the whole cohort. Patients were followed from diagnosis until death or last known alive (mean follow-up 7.9 years). The 10-year actuarial cumulative survival was 65.1% for women in the lowest quartile of serum selenium, compared to 86.7% for women in the highest quartile ( < 0.001 for difference). Further studies are needed to confirm the protective effect of selenium on breast cancer survival. If confirmed this may lead to an investigation of selenium supplementation on survival of breast cancer patients.
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http://dx.doi.org/10.3390/nu13030953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998294PMC
March 2021

Frequency of Contralateral Prophylactic Mastectomy in Breast Cancer Patients with a Negative BRCA1 and BRCA2 Rapid Genetic Test Result.

Ann Surg Oncol 2021 Mar 24. Epub 2021 Mar 24.

Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.

Background: There is an increasing desire for contralateral prophylactic mastectomy (CPM) among patients with unilateral breast cancer. It is unknown if risk assessment and genetic testing at the time of diagnosis will aid women in their surgical choice. We report on the uptake and predictors of CPM in women receiving a negative genetic test result for BRCA1 and BRCA2 mutations before surgery.

Methods: Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. Genetic counseling (risk assessment) and genetic testing was performed prior to surgery. Women were asked about their surgical preference before surgery. At 1 year post-surgery we asked what surgery was completed. This study reports on women who received a negative BRCA1/BRCA2 result.

Results: A total of 766 women with a mean age of 46 years (range 21-82) were included in the analysis. Before genetic counseling and testing, 37% of the women were undecided or leaning towards CPM; however, after receiving a negative BRCA test, 15% of the women opted for CPM. Thirty percent of women whose mother died of breast cancer elected for CPM, compared with 15% of women whose mother did not die of breast cancer (p = 0.03).

Conclusions: Women receiving a risk assessment and negative BRCA1/BRCA2 genetic test result before surgery use this information to guide their surgical decision. Uptake of CPM for women who were planning on CPM before genetic testing decreases after receiving a negative BRCA1/BRCA2 genetic test result.
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http://dx.doi.org/10.1245/s10434-021-09855-6DOI Listing
March 2021

Recurrent Mutations in , , , and in Polish Patients with Ovarian Cancer.

Cancers (Basel) 2021 Feb 18;13(4). Epub 2021 Feb 18.

Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland.

The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in , , , , and genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in (9 mutations), (4 mutations), (3 mutations), (2 mutations), and (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in (OR = 40.79, 95% CI: 18.67-114.78; = 0.29 × 10), in (OR = 25.98; 95% CI: 1.55-434.8; = 0.001), in (OR = 6.28; 95% CI 1.77-39.9; = 0.02), and in (OR 3.34; 95% CI: 1.06-14.68; = 0.06). There was no association found for We found that pathogenic mutations in , , or are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.
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http://dx.doi.org/10.3390/cancers13040849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921976PMC
February 2021

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.

JAMA Netw Open 2021 03 1;4(3):e210307. Epub 2021 Mar 1.

Sylvester Comprehensive Cancer Center, Miami, Florida.

Importance: Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population.

Objective: To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations.

Design, Setting, And Participants: This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020.

Exposures: Breast and/or ovarian cancer diagnosis.

Main Outcomes And Measures: Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants.

Results: Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P < .001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P = .001).

Conclusions And Relevance: In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921902PMC
March 2021

Survival from breast cancer in women with a BRCA2 mutation by treatment.

Br J Cancer 2021 Apr 18;124(9):1524-1532. Epub 2021 Feb 18.

Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.

Background: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.

Methods: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.

Results: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56).

Conclusions: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.
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http://dx.doi.org/10.1038/s41416-020-01164-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076275PMC
April 2021

Bilateral Mastectomy in Women With Unilateral Breast Cancer: A Review.

JAMA Surg 2021 Jun;156(6):569-576

Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

Importance: Rates of bilateral mastectomy continue to increase in average-risk women with unilateral in situ and invasive breast cancer. Contralateral prophylactic mastectomy rates increased from 5% to 12% of all operations for breast cancer in the US from 2004 to 2012. Among women having mastectomy, rates of contralateral prophylactic mastectomy have increased from less than 2% in 1998 to 30% in 2012.

Observations: The increased use of breast magnetic resonance imaging and genetic testing has marginally increased the number of candidates for bilateral mastectomy. Most bilateral mastectomies are performed on women who are at no special risk for contralateral cancer. The true risk of contralateral breast cancer is not associated with the decision for contralateral prophylactic mastectomy; rather, the clinical factors associated with the probability of distant recurrence are associated with bilateral mastectomy. Several changes in society and health care delivery appear to act concurrently and synergistically. First, the anxiety engendered by a fear of cancer recurrence is focused on the contralateral cancer because this is most easily conceptualized and provides a ready target that can be acted upon. Second, the modern woman with breast cancer is supported by the surgeon and the social community of breast cancer survivors. Surgeons want to respect patient autonomy, despite guidelines discouraging bilateral mastectomy, and most women have their expenses covered by a third-party payer. Satisfaction with the results is high, but the association with improved psychosocial well-being remains to be fully understood.

Conclusions And Relevance: Reducing the use of medically unnecessary contralateral prophylactic mastectomy in women with nonhereditary, unilateral breast cancer requires a social change that addresses patient-, physician-, cultural-, and systems-level enabling factors. Such a transformation begins with educating clinicians and patients. The concerns of women who want preventive contralateral mastectomy must be explored, and women need to be informed of the anticipated benefits (or lack thereof) and risks. Areas requiring further study are considered.
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http://dx.doi.org/10.1001/jamasurg.2020.6664DOI Listing
June 2021

Which Genes for Hereditary Breast Cancer?

Authors:
Steven A Narod

N Engl J Med 2021 02 20;384(5):471-473. Epub 2021 Jan 20.

From the Women's College Research Institute, Toronto.

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http://dx.doi.org/10.1056/NEJMe2035083DOI Listing
February 2021

Countercurrents: The Last Trial.

Authors:
Steven A Narod

Curr Oncol 2021 01 5;28(1):275-277. Epub 2021 Jan 5.

Women's College Research Institute, Women's College Hospital, Toronto, ON M5S 1B2, Canada.

If you have been around long enough, you will have heard more than once that an important clinical question is about to be resolved by a study that is soon to be published [...].
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http://dx.doi.org/10.3390/curroncol28010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903276PMC
January 2021

Breast cancer risk after age 60 among BRCA1 and BRCA2 mutation carriers.

Breast Cancer Res Treat 2021 Jun 10;187(2):515-523. Epub 2021 Jan 10.

Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.

Purpose: It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80.

Methods: Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk.

Results: Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk.

Conclusions: Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.
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http://dx.doi.org/10.1007/s10549-020-06072-9DOI Listing
June 2021

The impacts of neoadjuvant chemotherapy and of cytoreductive surgery on 10-year survival from advanced ovarian cancer.

Int J Gynaecol Obstet 2021 Jun 13;153(3):417-423. Epub 2021 Jan 13.

Division of Gynecologic Oncology, Princess Margaret Cancer Center, University Health Networks, Toronto, ON, Canada.

Objective: To compare the long-term survival outcomes for women with advanced ovarian cancer treated with chemotherapy either before or after surgery (neoadjuvant chemotherapy vs primary cytoreductive surgery) at a single tertiary cancer center.

Methods: Retrospective cohort study of 326 patients with Stage IIIC or IV high-grade serous ovarian cancer who received neoadjuvant chemotherapy or primary cytoreductive surgery between 2001 and 2011. Clinical treatments were recorded and 10-year survival rates were measured.

Results: A total of 183 women (56.1%) underwent primary cytoreductive surgery and 143 women (43.9%) received neoadjuvant chemotherapy. Women who received neoadjuvant chemotherapy were more likely to have no residual disease than those who underwent primary cytoreductive surgery (51.4% vs 41.5%; P = 0.030) but experienced inferior 10-year overall survival (9.1% vs 19.3%; P < 0.001). Among those who had primary cytoreductive surgery, those with no residual disease had superior 10-year overall survival than those who had any evidence of residual disease (36.0% vs 7.2%; P < 0.001).

Conclusion: Among women with advanced ovarian cancer, those who underwent primary cytoreductive surgery had better survival than those who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy should be reserved for those in whom optimal primary cytoreductive surgery is not feasible.
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http://dx.doi.org/10.1002/ijgo.13542DOI Listing
June 2021

CA125 and Ovarian Cancer: A Comprehensive Review.

Cancers (Basel) 2020 Dec 11;12(12). Epub 2020 Dec 11.

Women's College Research Institute, University of Toronto, Toronto, ON M5S 1B2, Canada.

Ovarian cancer is the second most lethal gynecological malignancy. The tumour biomarker CA125 has been used as the primary ovarian cancer marker for the past four decades. The focus on diagnosing ovarian cancer in stages I and II using CA125 as a diagnostic biomarker has not improved patients' survival. Therefore, screening average-risk asymptomatic women with CA125 is not recommended by any professional society. The dualistic model of ovarian cancer carcinogenesis suggests that type II tumours are responsible for the majority of ovarian cancer mortality. However, type II tumours are rarely diagnosed in stages I and II. The recent shift of focus to the diagnosis of low volume type II ovarian cancer in its early stages of evolution provides a new and valuable target for screening. Type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours. The detection of low volume type II carcinomas in stage IIIa/b is associated with a higher likelihood for optimal cytoreduction, the most robust prognostic indicator for ovarian cancer patients. The diagnosis of type II ovarian cancer in the early substages of stage III with CA125 may be possible using a higher cutoff point rather than the traditionally used 35 U/mL through the use of point-of-care CA125 assays in primary care facilities. Rapid point-of-care testing also has the potential for effective longitudinal screening and quick monitoring of ovarian cancer patients during and after treatment. This review covers the role of CA125 in the diagnosis and management of ovarian cancer and explores novel and more effective screening strategies with CA125.
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http://dx.doi.org/10.3390/cancers12123730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763876PMC
December 2020

Blood cadmium levels as a marker for early lung cancer detection.

J Trace Elem Med Biol 2021 Mar 12;64:126682. Epub 2020 Nov 12.

Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra (Szczecińska), Poland. Electronic address:

Background: We assessed whether blood cadmium levels were associated with incident lung cancer and could be used in the context of a screening program for early-stage lung cancer.

Material And Methods: We measured blood cadmium levels among 205 lung cancer patients and 205 matched controls. Cases and controls were matched for sex, age and smoking history (total pack-years, years since cessation for former smokers).

Results: The odds ratio for those in the highest quartile of cadmium level (versus lowest) was four-fold (OR = 4.41, 95 % CI:2.01-9.67, p < 0.01). The association was present in former smokers (OR = 16.8, 95 % CI:3.96-71.2, p < 0.01), but not in current smokers (OR = 1.23, 95 % CI: 0.34-4.38) or in never smokers (OR not defined). Among former smokers, the association was present in both early- and late-stage lung cancer.

Conclusion: Blood cadmium levels may be a marker to help with the early detection of lung cancer among former smokers.
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http://dx.doi.org/10.1016/j.jtemb.2020.126682DOI Listing
March 2021

Breast Cancer Mortality among Women with a or Mutation in a Magnetic Resonance Imaging Plus Mammography Screening Program.

Cancers (Basel) 2020 Nov 23;12(11). Epub 2020 Nov 23.

Women's College Research Institute, University of Toronto, Toronto, ON M5G 1N8, Canada.

Annual breast magnetic resonance imaging (MRI) plus mammography is the standard of care for screening women with inherited mutations. However, long-term breast cancer-related mortality with screening is unknown. Between 1997 and June 2011, 489 previously unaffected mutation carriers aged 25 to 65 years were screened with annual MRI plus mammography on our study. Thereafter, participants were eligible to continue MRI screening through the high-risk Ontario Breast Screening Program. In 2019, our data were linked to the Ontario Cancer Registry of Cancer Care Ontario to identify all incident cancers, vital status and causes of death. Observed breast cancer mortality was compared to expected mortality for age-matched women in the general population. There were 91 women diagnosed with breast cancer (72 invasive and 19 ductal carcinoma in situ (DCIS)) with median follow-up 7.4 (range: 0.1 to 19.2) years. Four deaths from breast cancer were observed, compared to 2.0 deaths expected (standardized mortality ratio (SMR) 2.0, = 0.14). For the 489 women in the study, the probability of not dying of breast cancer at 20 years from the date of the first MRI was 98.2%. Annual screening with MRI plus mammography is a reasonable option for women who decline or defer risk-reducing mastectomy.
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http://dx.doi.org/10.3390/cancers12113479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700272PMC
November 2020

The relationship between the predicted risk of death and psychosocial functioning among women with early-stage breast cancer.

Breast Cancer Res Treat 2021 Feb 10;186(1):177-189. Epub 2020 Nov 10.

Women's College Research Institute, Women's College Hospital, 76 Grenville St., 6th Floor, Toronto, ON, M5S 1B2, Canada.

Purpose: Many women with early-onset breast cancer experience adverse psychological sequelae which impact on their quality of life. We sought to correlate levels of anxiety and cancer-related distress in women with breast cancer shortly after surgery and one year after treatment with the estimated risk of death.

Methods: We studied 596 women with Stage I to III breast cancer. For each woman we estimated the five-year risk of death based on SEER data from 2010 to 2019. For each woman we measured anxiety and cancer-related distress levels shortly after surgery and one year later.

Results: The mean estimated five-year survival was 95%. At one week post-surgery, 59% of women had a clinically significant level of anxiety and 74% had a clinically significant level of cancer-related distress. There was no correlation between the objective risk of death and the level of anxiety or distress, at one week or at one year.

Conclusions: Many women diagnosed with early-stage breast cancers experience significant levels of anxiety and distress. The emotional response to a breast cancer diagnosis is not related to the risk of death per se and other factors should be explored.
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http://dx.doi.org/10.1007/s10549-020-05992-wDOI Listing
February 2021

Mammography screening for breast cancer-the UK Age trial.

Authors:
Steven A Narod

Lancet Oncol 2020 11;21(11):e508

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Women's College Research Institute, Women's College Hospital, Toronto, ON, M5S 1B2, Canada. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(20)30490-3DOI Listing
November 2020

In Response to "Pregnancy After Breast Cancer in Patients With Germline Mutations".

J Clin Oncol 2020 12 30;38(36):4352. Epub 2020 Oct 30.

Steven A. Narod, MD, and Vasily Giannakeas, MPH, Dalla Lana School of Public Health, University of Toronto; and Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1200/JCO.20.02253DOI Listing
December 2020

Survival Differences in Chinese Versus White Women With Breast Cancer in the United States: A SEER-Based Analysis.

JCO Glob Oncol 2020 10;6:1582-1592

Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

Purpose: The affect of race on breast cancer prognosis is not well understood. We compared crude and adjusted breast cancer survival rates of Chinese women versus White women in the United States.

Methods: We conducted a cohort study of Chinese and White women with breast cancer diagnosed between 2004 to 2015 in the SEER 18 registries database. We abstracted information on age at diagnosis, tumor size, grade, lymph node status, receptor status, surgical treatment, receipt of radiotherapy and chemotherapy, and death. We compared crude breast cancer-specific mortality between the two ethnic groups. We calculated adjusted hazard ratios (HRs) in a propensity-matched design using the Cox proportional hazards model. < .05 was considered statistically significant.

Results: There were 7,553 Chinese women (1.8%) and 414,618 White women (98.2%) with stage I-IV breast cancer in the SEER database. There were small differences in demographics, nodal burden, and clinical stage between Chinese and White women. Ten-year breast cancer-specific survival was 88.8% for Chinese women and 85.6% for White women (HR, 0.73; 95% CI, 0.67 to 0.80; < .0001). In a propensity-matched analysis among women with stage I-IIIC breast cancer, the HR was 0.71 (95% CI, 0.62 to 0.81; < .0001). Annual mortality rates in White women exceeded those in Chinese women for the first 9 years after diagnosis.

Conclusion: Chinese women in the United States have superior breast cancer-specific survival compared with White women. The reason for the observed difference is not clear. Differences in demographic and tumor features between Chinese and White women with breast cancer may contribute to the disparity, as may the possibility of intrinsic biologic differences.
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http://dx.doi.org/10.1200/GO.20.00316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605368PMC
October 2020

Preferences for breast cancer prevention among women with a or mutation.

Hered Cancer Clin Pract 2020 29;18:20. Epub 2020 Sep 29.

AbbVie Inc, Dublin, Ireland.

Background: Women with a or mutation have high lifetime risks of developing breast and ovarian cancer. The decision to embark on risk reduction strategies is a difficult and personal one. We surveyed an international group of women with mutations and measured choices and sequence of breast cancer risk reduction strategies.

Methods: Women with a mutation and no previous cancer diagnosis were recruited from the US, Canada, the UK, Australia, and from a national advocacy group. Using an online survey, we asked about cancer-risk reduction preferences including for one of two hypothetical medicines, randomly assigned, and women's recommendations for a hypothetical woman (Susan, either a 25- or 36-year-old). Sunburst diagrams were generated to illustrate hierarchy of choices.

Results: Among 598 respondents, mean age was 40.9 years (range 25-55 years). Timing of the survey was 4.8 years (mean) after learning their positive test result and 33% had risk-reducing bilateral salpingo-oophorectomy (RRBSO) and bilateral mastectomy (RRBM), while 19% had RRBSO only and 16% had RRBM only. Although 30% said they would take a hypothetical medicine, 6% reported taking a medicine resembling tamoxifen. Respondents were 1.5 times more likely to select a hypothetical medicine for risk reduction when Susan was 25 than when Susan was 36. Women assigned to 36-year-old Susan were more likely to choose a medicine if they had a family member diagnosed with breast cancer and personal experience taking tamoxifen.

Conclusions: Women revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women with or mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical.
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http://dx.doi.org/10.1186/s13053-020-00152-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526374PMC
September 2020

Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 mutation.

Gynecol Oncol 2020 12 30;159(3):820-826. Epub 2020 Sep 30.

Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Electronic address:

Objective: BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation.

Method: Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures.

Results: A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37-0.58; P < 0.0001).

Conclusions: These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.
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http://dx.doi.org/10.1016/j.ygyno.2020.09.037DOI Listing
December 2020

Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone.

JAMA Netw Open 2020 10 1;3(10):e2013929. Epub 2020 Oct 1.

Division of Urology, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada.

Importance: The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis.

Objective: To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population.

Design, Setting, And Participants: This population-based cohort study included 173 580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020.

Exposures: Treatment combinations of radiation, chemotherapy, and surgery.

Main Outcome And Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model.

Results: Of 173 580 patients, most were men (125 080 [72.1%]), and the largest group was aged between 60 and 69 years (58 346 [33.6%]). Most patients had genitourinary cancer (86 235 [51.4%]) or colorectal cancer (69 241 [39.9%]). Overall, 64 301 (37.1%) received surgery alone, 51 220 (29.5%) received radiation alone, 15 624 (9.0%) were treated with radiation and chemotherapy, 15 252 (8.8%) received radiation with surgery, and 11 822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51 220) and radiation with chemotherapy (40 of 15 624), 0.2% among those who received radiation and surgery (36 of 15 252) and all 3 modalities (25 of 11 822), and 0.1% among those who received surgery with chemotherapy (13 of 14 861) and surgery alone (80 of 64 801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01; P < .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12; P < .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46; P < .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58; P < .001). In the general population, 7987 events occurred during 46 554 803 person-years (17.2 events per 100 000 person-years). The standardized incidence ratio for sarcoma among patients treated with radiation compared with the general population was 2.41 (95% CI, 1.57-3.69; 41.3 events per 100 000 person-years). The annual number of cases of sarcoma increased from 2009 (15 per 100 000 persons) to 2016 (32 per 100 000 persons), but the annual rate did not change during the study period.

Conclusions And Relevance: In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma. Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.13929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532387PMC
October 2020

Rapid Genetic Testing for BRCA1 and BRCA2 Mutations at the Time of Breast Cancer Diagnosis: An Observational Study.

Ann Surg Oncol 2021 Apr 28;28(4):2219-2226. Epub 2020 Sep 28.

Women's College Research Institute, Toronto, Canada.

Background: This study aimed to evaluate the impact of rapid genetic testing (RGT) for BRCA1 and BRCA2 at the time of breast cancer diagnosis on treatment choices. Bilateral mastectomy for the treatment of breast cancer in women with a BRCA1 or BRCA2 mutation offers a reduction in the risk of contralateral breast cancer. It is unclear whether offering RGT at the time of breast cancer diagnosis has an impact on women's surgical decision-making.

Methods: Women with breast cancer diagnosed between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. The participants completed a questionnaire before genetic testing, then one week and one year after disclosure of the genetic test result. Before surgery, RGT was performed. Diagnostic, pathologic, and treatment data were compared between those with and those without a BRCA mutation.

Results: The study enrolled 1007 women who consented to RGT. The mean age of the participants was 46.3 years, and the median time to result disclosure was 10 days. A BRCA mutation was found in 6% of the women. The women with a BRCA mutation were significantly more likely to elect for bilateral mastectomy than the women without a BRCA mutation (p < 0.0001). Of the BRCA-positive patients, 95.7% reported that they used their genetic test result to make a surgical decision.

Conclusions: The women provided with RGT at the time of breast cancer diagnosis use the genetic information to make treatment decisions, and the majority of those identified with a BRCA mutation elect for a bilateral mastectomy.
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http://dx.doi.org/10.1245/s10434-020-09160-8DOI Listing
April 2021

Patient reported experiences following laparoscopic prophylactic bilateral salpingo-oophorectomy or salpingectomy in an ambulatory care hospital.

Fam Cancer 2021 04 23;20(2):103-110. Epub 2020 Sep 23.

Women's College Research Institute, Women's College Hospital, 76 Grenville Street, Room 6423, Toronto, ON, M5S 1B2, Canada.

Women at risk of developing ovarian cancer because of a BRCA1 or BRCA2 pathogenic variant are candidates for prophylactic bilateral salpingo-oophorectomy (BSO). While BSO surgeries are routinely performed, to our knowledge there are no studies that have examined patient-reported experiences following laparoscopic BSO performed in an ambulatory care setting. The objective of this study was to examine whether women undergoing prophylactic laparoscopic BSO felt they were adequately informed about post-operative outcomes. A telephone interview was conducted among 46 women undergoing laparoscopic BSO to collect detailed information regarding surgical outcomes, complications, symptoms, and time to return to daily activities. The average age at surgery was 45.0 years (range 34-66) and 67% of women underwent BSO prior to age 50. The mean reported hospital stay was 7.2 h (range 4-12 h) and at time of discharge, 78% of the women felt well enough to go home. None of the women required a readmission to hospital. Forty-three percent (n = 20) of the women did not feel well informed about what to expect post-operatively. Most of the patient-reported outcomes (including pain, vaginal bleeding, and nausea/vomiting) were expected and patient-reported menopausal symptoms were more common among women who were premenopausal at surgery. In terms of returning to regular activities, premenopausal women (n = 36) resumed sexual activity on average at 43 days (range 2-365), which is later than postmenopausal women (n = 15) at 19 days (range 7-30). On average, women returned to full-time work in 16 days (range 1-56 days). Despite patients receiving pre-surgery counselling, our findings suggest that there is a need to provide supplemental, reinforcing patient materials in preparing patients for what to expect after surgery.
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http://dx.doi.org/10.1007/s10689-020-00208-yDOI Listing
April 2021

Breast cancer survival in Nordic BRCA2 mutation carriers-unconventional association with oestrogen receptor status.

Br J Cancer 2020 11 17;123(11):1608-1615. Epub 2020 Sep 17.

Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland.

Background: The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers.

Methods: We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression.

Results: About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) (P < 0.001). The survival analysis included 584 patients. Positive ER status was protective in the first 5 years from diagnosis (multivariate HR = 0.49; 95% CI 0.26-0.93, P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07-3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26-4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11-3.59, P = 0.02).

Conclusions: The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.
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http://dx.doi.org/10.1038/s41416-020-01056-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686356PMC
November 2020

Association of a Diagnosis of Ductal Carcinoma In Situ With Death From Breast Cancer.

JAMA Netw Open 2020 09 1;3(9):e2017124. Epub 2020 Sep 1.

Women's College Research Institute, Toronto, Ontario, Canada.

Importance: It is not clear to what extent a diagnosis of ductal carcinoma in situ (DCIS) impacts a woman's lifetime risk of dying of breast cancer. Under ideal circumstances, treatment will eliminate the risk of invasive ipsilateral recurrence and prevent subsequent mortality from breast cancer. The risk of dying of breast cancer after a diagnosis of DCIS had not been compared with that of women without cancer in the general population.

Objective: To determine the risk of death from breast cancer in a large cohort of patients treated for DCIS and to compare the risk with that of women in the general population.

Design, Setting, And Participants: This cohort study included data for women who had first primary DCIS diagnosed between 1995 and 2014 from the Surveillance, Epidemiology and End Results (SEER) registries database. Women with DCIS underwent surgical treatment, and approximately half also received radiotherapy. These women were followed from the date of DCIS diagnosis until death from breast cancer or date of last follow-up. Women in the general population without breast cancer were analyzed as controls. Follow-up information was available up to December 2016. The data were analyzed in March 2020.

Exposures: Patients with DCIS who underwent surgical treatment.

Main Outcomes And Measures: Breast cancer death was the main outcome. Standardized mortality ratios were estimated by comparing deaths from breast cancer among women diagnosed with DCIS with expected deaths from breast cancer among women in the general population who did not have cancer. Expected probability of death from breast cancer in the general population was calculated by an incidence-based mortality approach using standardized SEER-based incidence and case-fatality rates. Probability of breast cancer death was estimated based on the assumption that a cancer-free control was cancer free on the date the woman with DCIS was diagnosed and was studied until the end of follow-up.

Results: A total of 144 524 women diagnosed with first primary DCIS were included (mean [SD] age at diagnosis, 57.4 [11.0] years). There were 1540 deaths from breast cancer in the cohort. Based on SEER-based incidence and case-fatality rates, 458 breast cancer deaths were expected in an equivalent number of cancer-free women from the general population with equal follow-up. The standardized mortality ratio for death from breast cancer among women with DCIS was 3.36 (95% CI, 3.20-3.53). The elevated risk of death persisted more than 15 years after diagnosis.

Conclusions And Relevance: In the population studied, the risk of dying of breast cancer was increased 3-fold after a diagnosis of DCIS. This suggests that our current treatment focus on preventing invasive recurrence is insufficient to eliminate all deaths from breast cancer after DCIS.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.17124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495235PMC
September 2020

Mutations in ATM, NBN and BRCA2 predispose to aggressive prostate cancer in Poland.

Int J Cancer 2020 11 11;147(10):2793-2800. Epub 2020 Sep 11.

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.

In designing national strategies for genetic testing, it is important to define the full spectrum of pathogenic mutations in prostate cancer (PCa) susceptibility genes. To investigate the frequency of mutations in PCa susceptibility genes in Polish familial PCa cases and to estimate gene-related PCa risks and probability of aggressive disease, we analyzed the coding regions of 14 genes by exome sequencing in 390 men with familial prostate cancer and 308 cancer-free controls. We compared the mutation frequencies between PCa cases and controls. We also compared clinical characteristics of prostate cancers between mutation carriers and noncarriers. Of the 390 PCa cases, 76 men (19.5%) carried a mutation in BRCA1, BRCA2, NBN, ATM, CHEK2, HOXB13, MSH2 or MSH6 genes. No mutations were found in BRIP1, PTEN, TP53, MLH1, PMS2 and SPOP. Significant associations with familial PCa risk were observed for CHEK2, NBN, ATM, and HOXB13. High-grade (Gleason 8-10) tumors were seen in 56% of BRCA2, NBN or ATM carriers, compared to 21% of patients who tested negative for mutations in these genes (OR = 4.7, 95% CI 2.0-10.7, P = .0003). In summary, approximately 20% of familial prostate cancer cases in Poland can be attributed to mutations in eight susceptibility genes. Carriers of mutations in BRCA2, NBN and ATM develop aggressive disease and may benefit from intensified screening and/or chemotherapy.
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http://dx.doi.org/10.1002/ijc.33272DOI Listing
November 2020