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Studies have shown that a significant number of eligible breast cancer patients are not offered genetic testing or referral to genetic counseling. To increase access to genetic testing in South Eastern Norway, testing has since 2014 been offered directly to breast cancer patients by surgeons and oncologists. This practice is termed “mainstreamed genetic testing”. The aim of this study was to investigate to what extent patients in South Eastern Norway are offered testing. Three hundred and sixty one patients diagnosed in 2016 and 2017 at one regional and one university hospital in South Eastern Norway were included. Data on whether the patients fulfilled the criteria, whether they had been offered testing and if they were tested were collected. In total, 26.6% (96/361) fulfilled the criteria for testing. Seventy five percent (69/92) of these were offered testing, and 71.7% (66/92) were tested. At the university hospital, 90.2% (37/41) of eligible patients were offered testing, and at the regional hospital 62.7% (32/51). Fifty two percent (12/23) of eligible patient not offered testing were younger than 50 years at time of diagnosis. As many as 95.4% (125/131) of all patients who were offered testing, wanted to be tested. The majority of patients who fulfilled the criteria were offered testing, supporting the practice of mainstreamed genetic testing. There were nevertheless differences in rates of testing between the hospitals that affected all groups of patients, indicating that genetic testing may not be equally accessible to all patients. We suggest that efforts should be made to increase aware- ness and improve routines for genetic testing of breast cancer patients in Norway. Keywords Genetic testing · BRCA · Breast cancer · Mainstreaming cancer genetics Abbreviations NBCG Norwegian Breast Cancer Group Ahus Akershus University HospitalOC Ovarian cancer BC Breast cancer OUH Oslo University Hospital EPR Electronic patient record TNBC Triple negative breast cancer IH Innlandet Hospital TSD Service for sensitive data VUS Variant of unknown clinical significance * Eli Marie Grindedal email@example.com Background Department of Medical Genetics, Oslo University Hospital, Oslo, Norway Germline pathogenic variants in BRCA1 and BRCA2 are Department of Surgery, Section of Breast and Endocrine associated with a high lifetime risk of breast and ovarian Surgery, Innlandet Hospital, Hamar, Norway cancer [1–3]. Identification of a pathogenic variant in one of Department of Breast and Endocrine Surgery, Akershus these genes in a woman diagnosed with breast cancer (BC) University Hospital, Lørenskog, Norway provides critical information for treatment decisions for her Health Services Research Unit, Akershus University current cancer [4–9]. In addition, future breast and ovarian Hospital, Lørenskog, Norway cancer may be prevented through risk-reducing mastectomy Institute of Clinical Medicine, University of Oslo, Oslo, and salpingo-oophorectomy in herself and her relatives who Norway may also carry the variant [10–12]. Genetic testing of these Department of Oncology, Section of Breast- and Endocrine Surgery, Oslo University Hospital, Oslo, Norway Vol.:(0123456789) 1 3 134 E. M. Grindedal et al. two genes is therefore increasingly offered to BC patients at within a “mainstreaming genetic testing” model. More spe- time of diagnosis or during treatment. cifically, we investigated how many BC patients that were In most countries, genetic testing is only offered to BC offered genetic testing, and how many of them that wanted patients with an a priori high risk of being a carrier of a to be tested. We also explored how many of the BC patients pathogenic variant, either because they have BC at a young who fulfilled the NBCG criteria were offered testing, and age (below 50 years), triple negative BC (TNBC), or because the clinical characteristics such as age at BC diagnosis and they have a family history of breast and/or ovarian cancer. family history of cancer of those who fulfilled the criteria The Norwegian Breast Cancer Group (NBCG) has devel- that were not offered testing. Data were collected for patients oped criteria for BRCA tes ting of BC patients based on such diagnosed during the first half of 2016 and 2017. risk factors (see Table 1) . Similar guidelines have been developed in other countries [14, 15]. However, several studies have demonstrated that a significant number of BC Methods patients who fulfill these criteria are neither offered genetic testing nor referred to genetic counseling [16–20]. Mainstreamed genetic testing in South Eastern We have recently estimated that about 39% of all BC Norway patients in the South-Eastern Norway Regional Health Authority (hereafter called South Eastern Norway) were All genetic analyses for hereditary cancer in South Eastern tested in 2014 and 2015 . However, we do not know Norway are done at Department of Medical Genetics (DMG) how many of the patients who fulfilled the criteria that were at Oslo University Hospital (OUH). In 2014, surgical depart- offered testing. Based on the previous studies on rates of ments at all hospitals in South Eastern Norway and DMG genetic testing, we suspect that also in Norway there may agreed that the treating surgeon or oncologist could offer be BC patients eligible for testing according to the NBCG newly diagnosed BC patients who fulfill the criteria, diag- criteria who are not offered testing. We also suspect that the nostic genetic testing of the BRCA genes without referring the rate of genetic testing of BC patients may be higher in South patient to genetic counseling prior to ordering the test. The Eastern Norway than the previous studies have shown. One aim of this procedural change was both to increase access to explanation might be that many of the previous studies report genetic testing for BC patients and to obtain test results in a observations from before 2010, and the awareness and avail- time that allowed the surgeon or oncologist to incorporate ability of genetic testing has increased significantly during the the results into treatment decisions. DMG developed writ- last 5 years. Another explanation may be that in South Eastern ten information and consent forms, and specialists in Medical Norway, genetic testing is offered directly to BC patients by Genetics, genetic counselors and molecular geneticists from the treating surgeon or oncologist as part of regular surgical DMG held informational meetings at all hospitals. Apart from and/or oncological health care, a model called “mainstreamed these meetings, surgeons and oncologists did not receive any genetic testing” . The patient is only referred to genetic specific training in medical genetics. Patients who wanted to counseling if a pathogenic variant or a variant of unknown be referred to genetic counseling before testing could still be clinical significance (VUS) is detected. This is different from referred. Patients who tested positive for a pathogenic variant the traditional model where genetic tests are ordered by spe- or a VUS would all be referred to genetic counseling. The cialists in medical genetics or genetic counselors and only patient’s family history of cancer should be recorded when she after genetic counseling. It has been argued that the traditional is admitted to the hospital for treatment. The treating physi- model contributes to keeping rates of genetic testing low . cian only offers testing of BRCA1 and BRCA2. Patients who The role of genetic testing in treatment of BC and other had a normal BRCA tes t but had a family history of cancer that cancers will increase in the coming years. This is both due indicated either testing of other genes, and/or that she or her to the decreasing costs associated with such testing, the relatives should be recommended follow up for familial risk increasing knowledge of different genes associated with of BC, would also be referred to genetic counseling. heritable cancer risk, and new opportunities for personal- ized treatment for hereditary tumors. Knowledge on how Patients the health service of genetic testing is practiced is therefore needed to ensure that testing is equally available to all eligi- The two hospitals involved in the study were Akershus Univer- ble patients across hospitals and health regions. sity Hospital (Ahus) and Innlandet Hospital Trust (IH). Ahus The aim of this study was to explore to what extent serves a population of 500.000 and IH a population of 380.000. genetic testing of BC patients is provided at two hospitals All patients diagnosed with invasive BC between 1st of in South Eastern Norway, one regional and one university January and 30th of June in 2016 and 2017 were identified, hospital. In both hospitals, genetic testing is offered directly 303 from Ahus and 256 from IH. These two time periods were to the patient by the treating surgeon or oncologist: i.e. chosen to uncover a potential increase in the use of genetic 1 3 Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway 135 Table 1 NBCG criteria for diagnostic genetic testing of breast cancer registered that it was uncertain whether the patient fulfilled patients in 2016 them. Finally, data was collected on whether or not the a patient had been offered genetic testing, if yes by whom, Woman with breast cancer < 50 years a and whether the patient had been tested. We also registered Two close r elatives with breast cancer, mean age < 55 years a whether it was the patient who had asked for the test.The Three close relatives with breast cancer at any age data were registered in a web based form and stored at the Male breast cancer Service for Sensitive Data (TSD, University of Oslo). No Woman with bilateral breast cancer < 60 years b demographic data like education level, employment status, Woman with breast cancer and a close relative with ovarian cancer ethnic background, marital or familial status were collected. Woman with breast cancer and a close relative with prostate can- In the consent form the patients could tick off that they cer < 55 years wanted to be contacted if they were eligible for genetic test- Woman with ovarian cancer at any age ing according to the criteria. Patients that ticked off the box Woman with triple negative breast cancer < 60 years (as recom- mended by the National Comprehensive Cancer Network, USA) and had not been tested before, but fulfilled the criteria in use in 2018, were contacted and offered testing. Patients who In 2018, the age limit for testing was raised to 60 years b could not be scored according to the criteria in use in 2018 Close relative is a first degree relative, or a second degree relative were contacted for evaluation of family history and offered through a man testing if they fulfilled the criteria. Included in the criteria from 2017 Non‑responders testing from 2016 to 2017, as there was a small change in the criteria in 2017 (see Table 1). All patients were sent an Ninety four BC patients at IH (36.7%) and 104 (34.3%) at information letter and a consent form to give access to their Ahus did not sign the consent form. Their mean age was 64 hospital records. One hundred and ninety nine BC patients and 60.6 years respectively. This is similar to the mean age from Ahus and 162 from IH signed the consent form, giving a of the patients included in the study. No other demographic response rate of 65.7% and 63.3% for the two hospitals respec- information was collected on the patients that did not sign tively. Mean age was similar for the two groups, 61.1 (range the consent form. 33–92) for Ahus and 60.4 (range 28–86) for IH. The distribu- tion of patients in different age groups was also similar for Statistics the two hospitals. See Table 2 for a description of the cohorts. We report descriptive statistics of our findings for the two Methods hospitals separately and combined, and present percentages of patients falling into the different categories investigated. Due We collected data on age at diagnosis, whether the patient to the limited size of the datasets, no statistical comparison had bilateral BC and whether the tumor was triple negative of the two hospitals was made. The results for 2016 and 2017 (ER, PR and HER2 negative) from the Electronic Patient were similar and were therefore combined in the analyses. Record (EPR). In addition, information was collected on whether the patient had been asked about their family his- Ethics tory of cancer, whether they had a family history of cancer and if yes, what type of cancers. The patients were then The research project was evaluated by the Regional Commit- scored according to the NBCG criteria used at time of diag- tees for Medical and Health Research Ethics. They defined nosis (see Table 1). When information in the EPR was not it as a quality of care study, and therefore outside of their sufficient to score the patient according to the criteria, we Table 2 Description of cohorts Innlandet hospital (n = 162) Ahus (n = 199) Combined (n = 361) Mean age 60.4 (range 28–86) 61.1 (range 33–92) 60.8 (range 28–92) Age cohorts 20–29 1 (0.6%) – 1 (0.3%) 30–39 5 (3.1%) 4 (2.0%) 9 (2.5%) 40–49 23 (14.2%) 27 (13.6%) 50 (13.9%) 50–59 48 (29.6%) 52 (26.1%) 100 (27.7%) 60–69 55 (34.0%) 77 (38.7%) 132 (36.6%) 70- 30 (18.5%) 39 (19.6%) 69 (19.1%) 1 3 136 E. M. Grindedal et al. mandate. The study has been approved by the data protection (95.4%). The test had been requested by the surgeon prior to officers at Oslo University Hospital (OUH), Ahus and IH. surgery in 71/125 (56.8%) of patients, and by the oncologist Informed consent was obtained from all individual partici- in 53/125 (42.4%). See Table 3. pants included in the study. Fulfillment of criteria Results Most of the patients who fulfilled the criteria for testing, did so due to young age at diagnosis (below 50 years): Twenty Results regarding use of genetic testing were similar for the nine out of 162 (17.9%) patients at IH and 31/199 (15.6%) two time periods investigated (first half of 2016 and first half at Ahus. It was noted in the medical records of 126/162 of 2017), and were therefore combined. (77.8%) patients at IH and 189/199 (95.0%) at Ahus that they had been asked about their family history. Of these, Genetic testing of all patients 18/126 (14.3%) patients at IH and 6/189 (3.2%) at Ahus fulfilled the criteria due to family history of cancer only (i.e. In one of the medical records from IH and four from Ahus it they did not have BC < 50 years/TNBC < 60 years/bilateral was noted that the patient had been tested prior to their BC BC < 60 years/male BC). See Table 3. diagnosis. These five patients were not offered a new test during diagnosis and treatment of their BC. Excluding them Genetic testing according to the NBCG criteria from the denominator, 131 of 356 patients (36.8%) had been tested, 48/161 (29.8%) at IH and 83/195 (42.6%) at Ahus. Of The results regarding genetic testing according to whether the 131 who were offered testing, 125 wanted to be tested or not the patient fulfilled the NBCG criteria can be found in Table 3 Genetic testing of Innlandet hospital Ahus (n = 199) Combined (n = 361) all patients and evaluation of (n = 162) criteria Genetic testing a a a Offered genetic testing n = 161 n = 195 n = 356 48 (29.8%) 83 (42.6%) 131 (36.8%) a a a Tested n = 161 n = 195 n = 356 45 (27.8%) 80 (40.2%) 125 (34.6%) Uptake of genetic testing n = 48 n = 83 n = 131 45 (93.8%) 80 (96.4%) 125 (95.4%) Test ordered by n = 45 n = 80 n = 125 Surgeon 23 (51.1%) 48 (60%) 71 (56.8%) Oncologist 22 (48.9%) 31 (38.8%) 53 (42.4%) Other 1 (1.3%) 1 (0.8%) Evaluation of family history Asked about family history of cancer n = 162 n = 199 n = 361 126 (77.8%) 189 (95.0%) 315 (87.3%) Reported family history of breast and/or n = 126 n = 189 n = 315 ovarian cancer 58 (46.0%) 66 (34.9%) 124 (39.4%) Criteria fulfilled BC < 50 years n = 162 n = 199 n = 361 29 (17.9%) 31 (15.6%) 60 (16.6%) Bilateral BC < 60 years n = 162 n = 199 n = 361 2 (1.2%) 2 (1%) 4 (1.1%) TNBC < 60 years n = 162 n = 199 n = 361 3 (1.9%) 3 (1.5%) 6 (1.7%) Male breast cancer – n = 199 n = 361 2 (1.0%) 2 (0.5%) Family history of BC and/or OC n = 126 n = 189 n = 315 18 (14.3%) 6 (3.2%) 24 (7.6%) Excluded patients who had been tested prior to their breast cancer diagnosis These patients were 50 years or older at time of diagnosis, and did not fulfill any of the other criteria (TNBC < 60 years, bilateral B < 60 years or male BC) 1 3 Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway 137 Fig. 1. In total, 96/361 (26.6%) patients fulfilled the NBCG at Ahus. At IH 18/31 (58.1%) had been tested by their sur- criteria. Four of these had been tested previously. Excluding geon, and 12/31 (38.7%) by their oncologist, while at Ahus, these, 69/92 (75%) of BC patients who fulfilled the criteria 25/35 (71.4%) were tested by their surgeon and 9/35 (25.7%) were offered testing, 32/51 (62.7%) at IH and 37/41 (90.2%) by their oncologist. Fig. 1 Genetic testing according to the criteria issued by the Norwegian Breast Cancer Group 1 3 138 E. M. Grindedal et al. Table 4 Number of BC patients Criteria Innlandet Hospital Ahus Combined offered testing according to what part of the NBCG criteria BC < 50 years 19/29 (65.2%) 28/30 (93.5%) 47/59 (79.7%) they fulfill Bilateral BC < 60 years 2/2 1/1 3/3 TNBC < 60 years 1/3 3/3 4/6 (66.7%) Family history of BC and/or OC* 10/17 (58.8%) 5/5 15/22 (68.2%) Male breast cancer – 0/2 0/2 *These patients were 50 years or above at time of diagnosis, and did not fulfill any of the other criteria (TNBC < 60 years, bilateral BC < 60 years or male BC Table 5 Characteristics of BC patients fulfilling criteria who were not testing has been mainstreamed into regular oncological care offered testing in South Eastern Norway since 2014. Even though the majority of eligible patients were offered Criteria fulfilled Patients (n = 23) testing during the study period, we observed differences BC < 50 12 (52.2%) between the hospitals, as 63% of eligible patients were TNBC < 60 2 (8.7%) offered testing at the regional hospital compared to 90% at Family history of BC and/or OC* 7 (30.4%) the university hospital. The lower rates were observed both Male BC 2 (8.7%) for the patients who fulfilled the criteria due to young age of onset and the older patients who had a family history of *These patients were 50 years or above at time of diagnosis, and did not fulfill any of the other criteria (TNBC < 60 years, bilateral cancer. Our data do not provide systematic information on BC < 60 years or male BC) why there was a difference between the two hospitals. At the university hospital, the EPR had a standardized format with headings that included the term “heredity”, whereas Scoring each of the 92 patients who fulfilled the NBCG the EPR at the regional hospital to a lesser degree seemed criteria according to what part of the criteria they fulfilled, to have a set structure with pre-defined headings. Having a and according to whether or not they had been offered test- set structure with headings will remind the clinician of ask- ing, 19 out of 29 patients (65.2%) diagnosed with BC below ing about family history and may also remind the clinicians 50 years at IH had been offered testing and 28/30 (93.5%) at of genetic testing. The observed difference may also be due Ahus. Of the patients who were 50 years or older at time of to differences in awareness and traditions regarding genetic diagnosis, and fulfilled the criteria only because they had a testing between the two hospitals. family history of BC and/or OC, 10/17 (58.8%) were offered We have previously estimated that 39% of all BC patients testing at IH and 5/5 at Ahus. None of the two men with BC in South Eastern Norway were tested in 2014 and 2015 . were offered testing (Table 4). Twelve of the 23 patients In the current study we found that 36.8% of all BC patients who fulfilled the criteria but were not offered testing (52.2%) (29.8% at IH and 42.6% at Ahus) were offered testing, and were under 50 years at time of diagnosis (Table 5). that 34.6% (27.8% at IH and 40.2% at Ahus) had been tested. The estimate from 2014 and 2015 covers all hospitals in South Eastern Norway (except from OUH) and numbers may Discussion vary between hospitals. Comparisons should therefore be made with caution, but the overall rates of testing may not This study is the first report of rates of genetic testing in have increased significantly since then. Norway. It includes observations from two hospitals and may For the two hospitals combined, as many as 52% of the provide important insight for the continuous work of making patients eligible for testing according to the NBCG criteria this health service available for all eligible BC patients. The who had not been offered testing, were young at time of main objective was to investigate to what extent BC patients diagnosis (below 50 years). Our data are based on informa- who fulfill the NBCG criteria were offered genetic testing, tion registered in the EPR. We cannot exclude that some of and we found that 75% of these patients were offered testing. these patients have been offered testing and declined, with- Other studies have reported testing rates ranging from 15.3% out it being noted. We also do not know whether they have to 60% [16–20]. The design of our study does not enable us a different demographic profile in terms of for example edu- to fully explain why we have observed such a high rate of cation level or marriage status compared to those that were testing compared to previous studies. We suspect that it may tested. Nevertheless, our observations indicate that, at the be due to the increasing awareness and availability of test- moment, not all young BC patients are offered testing and ing during the last 10 years, but also to the fact that genetic there may be discrepancies between hospitals in the extent to 1 3 Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway 139 which the health service reaches this group of patients. Stud- we cannot rule out that there may be information relevant ies have shown that 5–10% of BC patients below 50 years for the study that was not recorded here. Some patients may have a pathogenic BRCA variant [21, 24]. Young carriers have been offered but have declined testing, without it being have many years ahead with an increased risk of contralat- noted, and family history could have been asked, but not eral BC and OC. They are the ones who will benefit the registered. In addition, we did not collect any demographic most from cancer prevention and hence, genetic testing. It data on the patients. The aim of this study was to investigate is therefore important that routines for genetic testing ensure to what extent the health care system is able to offer genetic that these patients have access to this health service. testing to BC patients according to clinical guidelines. It is There were only two male BC patients in our cohort, but a small study, including data from only two hospitals, and none of them were offered testing. We cannot generalize demographic factors were considered to be less relevant. based on these two men, but it should be emphasized in the Some studies have demonstrated that factors such as ethnic- guidelines that male BC patients have an approximately 10% ity, education level and income may affect rates of referral to risk of carrying a germline pathogenic BRCA variant, and genetic counseling and testing [32–35]. These studies have should therefore be offered testing [reviewed in 25]. not been restricted to newly diagnosed BC patients. Other As many as 95% of the patients who were offered testing studies have reported that access to testing is more affected wanted to be tested, demonstrating that this a health ser- by barriers on a provider or system level [36–39].We do vice that BC patients want. In contrast, in the DNA-BONus not know whether the eligible patients that were not offered study, only 45.4% of BC patients who were offered testing testing had a different demographic profile than the patients completed the test. In this study, all breast and ovarian can- who were offered testing. Based on the information that was cer patients diagnosed between 2012 and 2015 at hospitals found in the EPR, we registered whether testing had been in the western part of Norway were offered BRCA testing initiated by the physician or the patient. For all but three of as part of a research project . We cannot rule out that all tested patients, the physician had initiated the discus- there are some selection biases in our study. Apart from this sion of testing, indicating that demographic factors could the difference might be explained by the already mentioned be of limited importance for those who did not get access increasing awareness of hereditary breast and ovarian cancer to testing, but we cannot confirm this. The response rate for among cancer patients during the last years, and especially inclusion in the study and access to medical records was after Angelina Jolie shared her story in May 2013 . 63.3% for the regional hospital and 65.7% for the university At Ahus and IH, 57% of all tests were requested by the sur- hospital. No second reminder was sent to the patients. We geon at time of diagnosis, and 42% by the oncologist during only have information about those who responded. Even if chemotherapy. It is not stated in the guidelines when genetic the response rate was similar for the two hospitals, we can- testing should be done, but because the majority of patients not exclude that the dataset may be skewed either towards meet the surgeon first, there is an understanding that it is those who have been offered testing and/or have accepted the surgeons who bear the main responsibility. It is therefore testing, towards those who were not offered testing and/or surprising that 42% of the patients were offered testing by did not go through with testing or affected by demographic their oncologist. Based on our findings we argue that there is factors. However, the two cohorts were similar in terms of a need for definitions and guidelines regarding when genetic age distribution, and also similar to the age distribution of testing should be offered, and also to ensure that patients who all BC patients in Norway . do not undergo chemotherapy are offered testing. According to the current NBCG criteria, the treating physician can offer BC patients testing of the two BRCA genes only. If the patients’ personal or family history of can- Conclusions cer indicates that other genes could be relevant, the patient should be referred to genetic counseling . Several stud- In conclusion, in two hospitals in South Eastern Norway ies have reported that offering BC patients testing of multi where diagnostic genetic testing is offered directly to BC gene panels results in clinical significant findings in other patients by their surgeon or oncologist, the majority of breast cancer genes [28–31]. Whether surgeons and oncolo- patients who fulfilled the criteria were offered testing. The gists also should offer multi gene panels to BC patients is a design of the study does not allow us to fully explain why the continuous discussion in Norway. Given that not all eligible rates are higher than what has been observed in other stud- patients are offered testing today, such an expansion may ies. We nevertheless suspect that mainstreaming genetic test- require more training in genetics for the health personnel ing into regular oncological care has contributed. The high involved in diagnostics and treatment of BC. rates of testing therefore support this change of practice. There are some limitations to our study. Firstly, our data However, there were important differences in rates of test - are based on information from patient records alone, and ing between the hospitals that affected all groups of patients. 1 3 140 E. M. Grindedal et al. This indicates that diagnostic genetic testing of BC patients References is not equally available to all patients. We have also observed 1. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper that 95% of BC patients who were offered testing wanted to JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice be tested. Based on our findings we therefore suggest that P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, eor ff ts should be made to increase awareness and knowledge Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thor- of, and improve routines for genetic testing among clini- lacius S, Eerola H, Nevanlinna H, Syrjäkoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF cians that in turn will contribute to make genetic testing an (2003) Average risks of breast and ovarian cancer associated with integral part of diagnosis and treatment of BC in Norway. BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Med Acknowledgements Open Access funding provided by Oslo University Genet 72:1117–1130 & Oslo University Hospital. The study was funded by The Norwe- 2. King MC, Marks JH, Mandell JB (2003) Breast and ovarian can- gian Cancer Society (Grant Number 194790–2017). The authors thank cer risks due to inherited mutations in BRCA1 and BRCA2. Sci- all the patients who have consented to inclusion in the study and the ence 302:643–646 administrative staff at the departments of surgery at Akershus Univer - 3. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij sity Hospital and Innlandet Hospital. The authors would also like to TM, Roos-Blom MJ et al (2017) Risks of breast, ovarian, and thank Professor Jan Norum for his important support and contributions contralateral breast cancer for BRCA1 and BRCA2 mutation to this study before he passed away. carriers. JAMA 317(23):2402–2416. h tt ps : //d o i. or g/1 0. 1 00 1/ jama.2017.7112 Author contributions All authors contributed to the study conception 4. Metcalfe K, Gershman S, Ghadirian P, Lynch HT, Snyder C, Tung and design. Material preparation, data collection and analysis were N, Kim-Sing C, Eisen A, Foulkes WD, Rosen B, Sun P, Narod SA performed by Eli Marie Grindedal and Kjersti Jørgensen. Data inter- (2014) Contralateral mastectomy and survival after breast cancer pretation was done by all authors. The first draft of the manuscript in carriers of BRCA1 and BRCA2 mutations: retrospective analy- was written by Eli Marie Grindedal and Kjersti Jørgensen. All authors sis. BMJ 348:g226. https ://doi.org/10.1136/bmj.g226 commented on previous versions of the manuscript. All authors read 5. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, and approved the final manuscript. Mortimer P, Swaisland H, Lau A, O’Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS (2009) Inhi- bition of poly(ADP-ribose) polymerase in tumors from BRCA Funding This study was funded by The Norwegian Cancer Society mutation carriers. N Engl J Med 361(2):123–134. h t t ps : / /d o i . (Grant Number 194790–2017). org/10.1056/NEJMo a0900 212 6. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel Compliance with ethical standards JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J (2010) Oral Conflicts of interest Eli Marie Grindedal has received a grant from poly(ADP-ribose) polymerase inhibitor olaparib in patients with The Norwegian Cancer Society (Grant Number 194790–2017). BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376(9737):235–244. https ://doi. Ethical approval The research project was evaluated by the Regional org/10.1016/S0140 -6736(10)60892 -6 Committees for Medical and Health Research Ethics in South Eastern 7. Stover DG, Winer EP (2015) Tailoring adjuvant chemotherapy Norway. They defined it as a quality of care study, and thereby outside regimens for patients with triple negative breast cancer. Breast of their mandate. The study has been approved by the data protection 24:S132–S135. https ://doi.org/10.1016/j.breas t.2015.07.032 officers at Oslo University Hospital (OUH), Ahus and IH. 8. Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, Hylands L, Riisnaes R, Forster M, Omlin A, Kreis- Informed consent Informed consent was obtained from all individual cher N, Thway K, Gevensleben H, Sun L, Loughney J, Chatterjee participants included in the study. M, Toniatti C, Carpenter CL, Iannone R, Kaye SB, de Bono JS, Wenham RM (2013) The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with Open Access This article is licensed under a Creative Commons Attri- sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol bution 4.0 International License, which permits use, sharing, adapta- 14(9):882–892. https ://doi.org/10.1016/S1470 -2045(13)70240 -7 tion, distribution and reproduction in any medium or format, as long 9. Rodler ET, Kurland BF, Griffin M, Gralow JR, Porter P, Yeh RF, as you give appropriate credit to the original author(s) and the source, Gadi VK, Guenthoer J, Beumer JH, Korde L, Strychor S, Kie- provide a link to the Creative Commons licence, and indicate if changes sel BF, Linden HM, Thompson JA, Swisher E, Chai X, Shep- were made. The images or other third party material in this article are erd S, Giranda V, Specht JM (2016) Phase I study of Veliparib included in the article’s Creative Commons licence, unless indicated (ABT-888) combined with Cisplatin and Vinorelbine in advanced otherwise in a credit line to the material. If material is not included in triple-negative breast cancer and/or BRCA mutation-associated the article’s Creative Commons licence and your intended use is not breast cancer. Clin Cancer Res 22(12):2855–2864. https ://doi. permitted by statutory regulation or exceeds the permitted use, you will org/10.1158/1078-0432.CCR-15-2137 need to obtain permission directly from the copyright holder. To view a 10. Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber copy of this licence, visit http://creativ ecommons .or g/licenses/b y/4.0/. 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Familial Cancer – Springer Journals
Published: Apr 30, 2020
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