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      International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation

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          Abstract

          Background

          Women with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017).

          Methods

          Eligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries. Subjects completed a questionnaire at the time of genetic testing, which included past use of cancer prevention options and screening tests. Biennial follow-up questionnaires were administered.

          Results

          Six-thousand two-hundred and twenty-three women were followed for a mean of 7.5 years. The mean age at last follow-up was 52.1 years (27–96 years) and 42.3% of the women had a prior diagnosis of breast cancer. In all, 27.8% had a prophylactic bilateral mastectomy and  64.7% had a BSO. Screening with breast MRI increased from 70% before 2009 to 81% at or after 2009. There were significant differences in uptake of all options by country.

          Conclusion

          For women who received genetic testing more recently, uptake of prophylactic mastectomy and breast MRI is significantly higher than those who received genetic testing more than 10 years ago. However, uptake of both BSO and breast MRI is not optimal, and interventions to increase uptake are needed.

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          Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.

          Timothy R Rebbeck, Henry Lynch, Susan L Neuhausen … (2002)
          Data concerning the efficacy of bilateral prophylactic oophorectomy for reducing the risk of gynecologic cancer in women with BRCA1 or BRCA2 mutations are limited. We investigated whether this procedure reduces the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. A total of 551 women with disease-associated germ-line BRCA1 or BRCA2 mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. We determined the incidence of ovarian cancer in 259 women who had undergone bilateral prophylactic oophorectomy and in 292 matched controls who had not undergone the procedure. In a subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who had undergone bilateral prophylactic oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least eight years. Six women who underwent prophylactic oophorectomy (2.3 percent) received a diagnosis of stage I ovarian cancer at the time of the procedure; two women (0.8 percent) received a diagnosis of papillary serous peritoneal carcinoma 3.8 and 8.6 years after bilateral prophylactic oophorectomy. Among the controls, 58 women (19.9 percent) received a diagnosis of ovarian cancer, after a mean follow-up of 8.8 years. With the exclusion of the six women whose cancer was diagnosed at surgery, prophylactic oophorectomy significantly reduced the risk of coelomic epithelial cancer (hazard ratio, 0.04; 95 percent confidence interval, 0.01 to 0.16). Of 99 women who underwent bilateral prophylactic oophorectomy and who were studied to determine the risk of breast cancer, breast cancer developed in 21 (21.2 percent), as compared with 60 (42.3 percent) in the control group (hazard ratio, 0.47; 95 percent confidence interval, 0.29 to 0.77). Bilateral prophylactic oophorectomy reduces the risk of coelomic epithelial cancer and breast cancer in women with BRCA1 or BRCA2 mutations.
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            Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination.

            Jane K. Hill, Martin Yaffe, Roberta Jong … (2004)
            Current recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every 6 months; however, many tumors are detected at a relatively advanced stage. Magnetic resonance imaging (MRI) and ultrasound may improve the ability to detect breast cancer at an early stage. To compare the sensitivity and specificity of 4 methods of breast cancer surveillance (mammography, ultrasound, MRI, and CBE) in women with hereditary susceptibility to breast cancer due to a BRCA1 or BRCA2 mutation. A surveillance study of 236 Canadian women aged 25 to 65 years with BRCA1 or BRCA2 mutations who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound at a single tertiary care teaching hospital between November 3, 1997, and March 31, 2003. On the day of imaging and at 6-month intervals, CBE was performed. Sensitivity and specificity of each of the 4 surveillance modalities, and sensitivity of all 4 screening modalities vs mammography and CBE. Each imaging modality was read independently by a radiologist and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 ductal carcinoma in situ). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. There was 1 interval cancer. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined. In BRCA1 and BRCA2 mutation carriers, MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone. Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation.
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              Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation.

              Hanne EJ Meijers-Heijboer, Bert N. van Geel, Wim van Putten … (2001)
              Women with a BRCA1 or BRCA2 mutation have a high risk of breast cancer and may choose to undergo prophylactic bilateral total mastectomy. We investigated the efficacy of this procedure in such women. We conducted a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation who were enrolled in a breast-cancer surveillance program at the Rotterdam Family Cancer Clinic. At the time of enrollment, none of the women had a history of breast cancer. Seventy-six of these women eventually underwent prophylactic mastectomy, and the other 63 remained under regular surveillance. The effect of mastectomy on the incidence of breast cancer was analyzed by the Cox proportional-hazards method in which mastectomy was modeled as a time-dependent covariate. No cases of breast cancer were observed after prophylactic mastectomy after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers developed in women under regular surveillance after a mean follow-up of 3.0+/-1.5 years (P=0.003; hazard ratio, 0; 95 percent confidence interval, 0 to 0.36). The actuarial mean five-year incidence of breast cancer among all women in the surveillance group was 17+/-7 percent. On the basis of an exponential model, the yearly incidence of breast cancer in this group was 2.5 percent. The observed number of breast cancers in the surveillance group was consistent with the expected number (ratio of observed to expected cases, 1.2; 95 percent confidence interval, 0.4 to 3.7; P=0.80). In women with a BRCA1 or BRCA2 mutation, prophylactic bilateral total mastectomy reduces the incidence of breast cancer at three years of follow-up.
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                Author and article information

                Contributors
                Steven A. Narod: +416-351-3765 , steven.narod@wchospital.ca
                Journal
                Journal ID (nlm-ta): Br J Cancer
                Journal ID (iso-abbrev): Br. J. Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Electronic): 11 April 2019
                Publication date (Print): 2 July 2019
                Volume: 121
                Issue: 1
                Pages: 15-21
                Affiliations
                [1 ]ISNI 0000 0004 0474 0188, GRID grid.417199.3, Women’s College Research Institute, ; Toronto, ON Canada
                [2 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Bloomberg, Faculty of Nursing, , University of Toronto, ; Toronto, ON Canada
                [3 ]Toronto-Sunnybrook Regional Cancer Center, Toronto, ON Canada
                [4 ]ISNI 0000 0001 1545 0811, GRID grid.412332.5, Division of Human Genetics, , The Ohio State University Medical Center, Comprehensive Cancer Center, ; Columbus, OH USA
                [5 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, , University of Toronto, ; Toronto, ON Canada
                [6 ]Juravinksi Cancer Centre, Hamilton, ON L8V 5C2 Canada
                [7 ]ISNI 0000 0004 0485 2091, GRID grid.416529.d, North York General Hospital, ; Toronto, ON Canada
                [8 ]Vanderbilt-Ingram Cancer Center/Vanderbilt University Medical Center, Nashville, TN USA
                [9 ]ISNI 0000 0004 1936 8876, GRID grid.254748.8, Hereditary Cancer Center, Creighton University School of Medicine, ; Omaha, NE USA
                [10 ]ISNI 0000 0000 9011 8547, GRID grid.239395.7, Beth Israel Deaconess Medical Center, ; Boston, MA USA
                [11 ]Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR
                [12 ]Department of Surgery, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong SAR
                [13 ]Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong SAR
                [14 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Department of Population Sciences, , Beckman Research Institute of City of Hope, ; Duarte, CA USA
                [15 ]ISNI 0000 0001 2152 9905, GRID grid.50956.3f, Department of Obstetrics and Gynecology, , Cedars-Sinai Medical Center, ; West Hollywood, CA USA
                [16 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Research Group Inherited Cancer, Department of Medical, Genetics, , Oslo University Hospital, ; Oslo, Norway
                [17 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Tumor Biology, , Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, ; Oslo, Norway
                [18 ]ISNI 0000 0000 9024 6397, GRID grid.412581.b, Center for Hereditary Tumors, HELIOS-Klinikum Wuppertal, , University of Witten-Herdecke, ; Wuppertal, Germany
                [19 ]ISNI 0000 0001 0675 4725, GRID grid.239578.2, Genomic Medicine Institute, Center for Personalised Genetic Healthcare, Cleveland Clinic, ; Cleveland, OH USA
                [20 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, City of Hope National Medical Center, ; Duarte, CA USA
                [21 ]ISNI 0000 0001 1411 4349, GRID grid.107950.a, International Hereditary Cancer Center, Department of Genetics and Pathology, , Pomeranian Medical University, ; Szczecin, Poland
                [22 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Dalla Lana School of Public Health, , University of Toronto, ; Toronto, ON Canada
                Article
                Publisher ID: 446
                DOI: 10.1038/s41416-019-0446-1
                PMC ID: 6738089
                PubMed ID: 30971774
                SO-VID: 64cc5afa-9bc7-41de-9364-5727bc8fc327
                Copyright © © Cancer Research UK 2019
                License:

                This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

                History
                Date received : 31 July 2018
                Date revision received : 15 March 2019
                Date accepted : 19 March 2019
                Funding
                Funded by: Steven A. Narod is the recipient of a Canada Research Chair (Tier I). This work was supported the Peter Gilgan Foundation.
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © Cancer Research UK 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer prevention,breast cancer
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer prevention, breast cancer

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