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Steven A. Narod - One of the best experts on this subject based on the ideXlab platform.
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Factors associated with use of hormone therapy after Preventive oophorectomy in BRCA mutation carriers.
Menopause (New York N.Y.), 2020Co-Authors: Javier César Mejía-gómez, Steven A. Narod, Beth Y. Karlan, Jacek Gronwald, Ping Sun, Leigha Senter, Nadine Tung, Wendy Wolfman, Rochelle Demsky, Joanne KotsopoulosAbstract:OBJECTIVE Bilateral salpingo-oophorectomy (oophorectomy) is recommended to women with a germline BRCA1 or BRCA2 mutation before natural menopause to prevent ovarian and fallopian tube cancer. The adverse effects of early surgical menopause are well established. Although many of the side effects can be ameliorated by the use of hormone therapy (HT); use of HT in this group of predominantly young patients remains suboptimal. The goal of this study was to identify the frequency of HT use, as well as predictors of HT uptake in BRCA mutation carriers who underwent Preventive oophorectomy before natural menopause. METHODS Eligible participants were identified from a longitudinal study of BRCA mutation carriers. We included premenopausal women with no personal history of cancer who underwent oophorectomy before age 50 and who had a minimum of 2 years of follow-up. Detailed information on HT use and other important variables was collected by a research questionnaire every 2 years. Descriptive statistics were used to evaluate the use of HT in various subgroups. RESULTS A total of 793 women with a BRCA1 or BRCA2 mutation were included in this analysis. The mean age at oophorectomy was 42 years (range 28-49). Sixty-one percent of the women reported using HT after oophorectomy. Factors associated with HT use included young age at surgery, a high level of education and Preventive Mastectomy. CONCLUSIONS The uptake of HT after oophorectomy in women with a BRCA1 or BRCA2 mutation varies by age, education, and surgical history. Clinician and patient awareness may lead to better utilization of HT in women who undergo oophorectomy at an early age to help mitigate the adverse effects associated with surgical menopause.
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A clinically structured and partnered approach to genetic testing in Trinidadian women with breast cancer and their families
Breast Cancer Research and Treatment, 2019Co-Authors: Talia Donenberg, Steven A. Narod, Sophia George, Jameel Ali, Gabriela Bravo, Karen Hernandez, Navin Sookar, Kimlin Tam Ashing, Mohammad R. Akbari, Judith HurleyAbstract:Introduction Breast cancer (BC) is the leading cause of cancer death in Caribbean women. Across the Caribbean islands, the prevalence of hereditary breast cancer among unselected breast cancer patients ranges from 5 to 25%. Moreover, the prevalence of BC among younger women and the high mortality in the Caribbean region are notable. This BC burden presents an opportunity for cancer prevention and control that begins with genetic testing among high-risk women. Measured response to positive genetic test results includes the number of Preventive procedures and cascade testing in family members. We previously reported data on an active approach to promote cascade testing in the Bahamas and report on Preventive procedures showing moderate uptake. Here, we describe a clinically structured and community-partnered approach to the dissemination and follow-up of genetic test results including family counseling for the promotion of risk mitigation strategies and cascade testing in our Trinidadian cohort of patients tested positive for BC predisposition genes. Methods As a part of our initial study of BC genetic testing in Trinidad and Tobago, all participants received pre-test counseling including three-generation pedigree and genetic testing for BRCA1/2, PALB2, and RAD51C. The study was approved by the University of Miami IRB and the Ethics Committee of the Ministry of Health, Trinidad and Tobago. We prospectively evaluated a clinically structured approach to genetic counseling and follow-up of BC mutation carriers in Trinidad and Tobago in 2015. The intervention consisted of (1) engaging twenty-nine BC patients with a deleterious gene mutation (probands), and (2) invitation of their at-risk relatives to attend to a family counseling session. The session included information on the meaning of their results, risk of inheritance, risk of cancer, risk-reduction options, offering of cascade testing to family members, and follow-up of proband decision-making over two years. Results Twenty-four of twenty-nine mutation carriers (82.8%) consented to enroll in the study. At initial pedigree review, we identified 125 at-risk relatives (ARR). Seventy-seven ARR (62%) attended the family counseling sessions; of these, 76 ARR (99%) consented to be tested for their family gene mutation. Genetic sequencing revealed that of the 76 tested, 35 (46%) ARR were carriers of their family mutation. The ARR received their results and were urged to take preventative measures at post-test counseling. At 2-year follow-up, 6 of 21 probands with intact breasts elected to pursue Preventive Mastectomy (28.5%) and 4 of 20 women with intact ovaries underwent RRSO (20%). Conclusions In Trinidad and Tobago, a clinically structured and partnered approach to our testing program led to a significant rate of proband response by completing the intervention counseling session, executing risk-reducing procedures as well as informing and motivating at-risk relatives, thereby demonstrating the utility and efficacy of this BC control program.
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A clinically structured and partnered approach to genetic testing in Trinidadian women with breast cancer and their families.
Breast cancer research and treatment, 2018Co-Authors: Talia Donenberg, Steven A. Narod, Sophia George, Jameel Ali, Gabriela Bravo, Navin Sookar, Kimlin Tam Ashing, Mohammad R. Akbari, Karen Gomez Hernandez, Judith HurleyAbstract:Breast cancer (BC) is the leading cause of cancer death in Caribbean women. Across the Caribbean islands, the prevalence of hereditary breast cancer among unselected breast cancer patients ranges from 5 to 25%. Moreover, the prevalence of BC among younger women and the high mortality in the Caribbean region are notable. This BC burden presents an opportunity for cancer prevention and control that begins with genetic testing among high-risk women. Measured response to positive genetic test results includes the number of Preventive procedures and cascade testing in family members. We previously reported data on an active approach to promote cascade testing in the Bahamas and report on Preventive procedures showing moderate uptake. Here, we describe a clinically structured and community-partnered approach to the dissemination and follow-up of genetic test results including family counseling for the promotion of risk mitigation strategies and cascade testing in our Trinidadian cohort of patients tested positive for BC predisposition genes. As a part of our initial study of BC genetic testing in Trinidad and Tobago, all participants received pre-test counseling including three-generation pedigree and genetic testing for BRCA1/2, PALB2, and RAD51C. The study was approved by the University of Miami IRB and the Ethics Committee of the Ministry of Health, Trinidad and Tobago. We prospectively evaluated a clinically structured approach to genetic counseling and follow-up of BC mutation carriers in Trinidad and Tobago in 2015. The intervention consisted of (1) engaging twenty-nine BC patients with a deleterious gene mutation (probands), and (2) invitation of their at-risk relatives to attend to a family counseling session. The session included information on the meaning of their results, risk of inheritance, risk of cancer, risk-reduction options, offering of cascade testing to family members, and follow-up of proband decision-making over two years. Twenty-four of twenty-nine mutation carriers (82.8%) consented to enroll in the study. At initial pedigree review, we identified 125 at-risk relatives (ARR). Seventy-seven ARR (62%) attended the family counseling sessions; of these, 76 ARR (99%) consented to be tested for their family gene mutation. Genetic sequencing revealed that of the 76 tested, 35 (46%) ARR were carriers of their family mutation. The ARR received their results and were urged to take preventative measures at post-test counseling. At 2-year follow-up, 6 of 21 probands with intact breasts elected to pursue Preventive Mastectomy (28.5%) and 4 of 20 women with intact ovaries underwent RRSO (20%). In Trinidad and Tobago, a clinically structured and partnered approach to our testing program led to a significant rate of proband response by completing the intervention counseling session, executing risk-reducing procedures as well as informing and motivating at-risk relatives, thereby demonstrating the utility and efficacy of this BC control program.
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The expected benefit of Preventive Mastectomy on breast cancer incidence and mortality in BRCA mutation carriers, by age at Mastectomy
Breast Cancer Research and Treatment, 2018Co-Authors: Vasily Giannakeas, Steven A. NarodAbstract:Purpose Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of Preventive Mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a Preventive Mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women. Methods The age-specific annual risks of developing breast cancer were used to estimate the actuarial risk of developing breast cancer by age 80 for women with a BRCA1 or BRCA2 mutation. The probability of developing breast cancer before age 80 was then modified to include competing causes of death, including from ovarian cancer. The mortality rate from breast cancer after a diagnosis of breast cancer was set at 2% annually for the first 10 years and then 1% annually for years ten to twenty. The incidence rate and mortality rate from ovarian cancer were based on published literature. We assumed that Preventive Mastectomy was associated with complete protection against subsequent breast cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) until age 80, according to the age at Mastectomy. Results The actuarial risk of developing breast cancer until age 80 was estimated to be 70.8%. The actual risk (incorporating competing risks) was 64.0%. The probability of being alive at age 80 by having a Mastectomy at age 25 increased by 8.7% (from 42.7 to 51.3%). The estimated benefit declined with age at Mastectomy; for surgery done at age 50 the improvement in survival to age 80 was much more modest (2.8% at age 80, from 42.7 to 45.5%). Conclusions Among BRCA mutation carriers, the mortality benefit of Preventive Mastectomy at age 25 is substantial, but the expected benefit declines rapidly with increasing age at surgery.
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The expected benefit of Preventive Mastectomy on breast cancer incidence and mortality in BRCA mutation carriers, by age at Mastectomy.
Breast cancer research and treatment, 2017Co-Authors: Vasily Giannakeas, Steven A. NarodAbstract:Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of Preventive Mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a Preventive Mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women. The age-specific annual risks of developing breast cancer were used to estimate the actuarial risk of developing breast cancer by age 80 for women with a BRCA1 or BRCA2 mutation. The probability of developing breast cancer before age 80 was then modified to include competing causes of death, including from ovarian cancer. The mortality rate from breast cancer after a diagnosis of breast cancer was set at 2% annually for the first 10 years and then 1% annually for years ten to twenty. The incidence rate and mortality rate from ovarian cancer were based on published literature. We assumed that Preventive Mastectomy was associated with complete protection against subsequent breast cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) until age 80, according to the age at Mastectomy. The actuarial risk of developing breast cancer until age 80 was estimated to be 70.8%. The actual risk (incorporating competing risks) was 64.0%. The probability of being alive at age 80 by having a Mastectomy at age 25 increased by 8.7% (from 42.7 to 51.3%). The estimated benefit declined with age at Mastectomy; for surgery done at age 50 the improvement in survival to age 80 was much more modest (2.8% at age 80, from 42.7 to 45.5%). Among BRCA mutation carriers, the mortality benefit of Preventive Mastectomy at age 25 is substantial, but the expected benefit declines rapidly with increasing age at surgery.
Josef M Penninger - One of the best experts on this subject based on the ideXlab platform.
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rankl rank from bone loss to the prevention of breast cancer
Open Biology, 2016Co-Authors: Verena Sigl, Laundette P Jones, Josef M PenningerAbstract:RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the Preventive strategy for BRCA1-mutation carriers includes Preventive Mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible Preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer.
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RANKL/RANK: from bone loss to the prevention of breast cancer
Open biology, 2016Co-Authors: Verena Sigl, Laundette P Jones, Josef M PenningerAbstract:RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the Preventive strategy for BRCA1-mutation carriers includes Preventive Mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible Preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer.
J De Greve - One of the best experts on this subject based on the ideXlab platform.
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the impact of proband mediated information dissemination in families with a brca1 2 gene mutation
Journal of Medical Genetics, 2004Co-Authors: Erica Sermijn, G Goelen, E Teugels, L Kaufman, M Bonduelle, Bart Neyns, Bruce Poppe, A De Paepe, J De GreveAbstract:Since the identification of the BRCA1 (17q21)1 and BRCA2 (13q12–13)2,3 genes as the major predisposition genes for hereditary breast and ovarian cancer (HBOC),4 genetic counselling and predictive testing has progressively been introduced and applied throughout the world. In many centres, the initial approach towards these families has been very cautious, mainly because of lack of prospective data on the effects of Preventive measures to be proposed for mutation carriers and the uncertainty of the psychological impact of this information within these families. In the Familial Cancer Clinic of the Vrije Universiteit Brussel (VUB), Belgium, a multidisciplinary team adopted a protocol of ‘non-directive’ counselling based on the international guidelines used for Huntington families.5 Non-directiveness is a form of counselling that includes the presentation of several options without recommending a specific choice, but in the context of this study, non-directiveness is rather focused on the way the counselling team behaves towards other family members. According to this aspect of the protocol, the proband is the major and initially unique interlocutor between the family and the familial cancer team as represented by the counsellor. The proband helps in establishing the family pedigree and is informed about the various aspects of HBOC and predictive genetic testing. After a mutation is found, the relevant information and availability of predictive testing is communicated to the remainder of the family, initially through the proband and subsequently through other family members who come forward for testing. In contrast to persons affected by Huntington’s disease, several options are available to mutation carriers, which can alter their outcome. Recently, prospective data on the effectiveness of some Preventive options have emerged, including the short term protection provided by Preventive Mastectomy compared with Preventive screening.6 The availability of effective screening and prophylactic treatment makes “the right …
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The impact of proband mediated information dissemination in families with a BRCA1/2 gene mutation
Journal of medical genetics, 2004Co-Authors: Erica Sermijn, G Goelen, E Teugels, L Kaufman, M Bonduelle, Bart Neyns, Bruce Poppe, A De Paepe, J De GreveAbstract:Since the identification of the BRCA1 (17q21)1 and BRCA2 (13q12–13)2,3 genes as the major predisposition genes for hereditary breast and ovarian cancer (HBOC),4 genetic counselling and predictive testing has progressively been introduced and applied throughout the world. In many centres, the initial approach towards these families has been very cautious, mainly because of lack of prospective data on the effects of Preventive measures to be proposed for mutation carriers and the uncertainty of the psychological impact of this information within these families. In the Familial Cancer Clinic of the Vrije Universiteit Brussel (VUB), Belgium, a multidisciplinary team adopted a protocol of ‘non-directive’ counselling based on the international guidelines used for Huntington families.5 Non-directiveness is a form of counselling that includes the presentation of several options without recommending a specific choice, but in the context of this study, non-directiveness is rather focused on the way the counselling team behaves towards other family members. According to this aspect of the protocol, the proband is the major and initially unique interlocutor between the family and the familial cancer team as represented by the counsellor. The proband helps in establishing the family pedigree and is informed about the various aspects of HBOC and predictive genetic testing. After a mutation is found, the relevant information and availability of predictive testing is communicated to the remainder of the family, initially through the proband and subsequently through other family members who come forward for testing. In contrast to persons affected by Huntington’s disease, several options are available to mutation carriers, which can alter their outcome. Recently, prospective data on the effectiveness of some Preventive options have emerged, including the short term protection provided by Preventive Mastectomy compared with Preventive screening.6 The availability of effective screening and prophylactic treatment makes “the right …
Vasily Giannakeas - One of the best experts on this subject based on the ideXlab platform.
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The expected benefit of Preventive Mastectomy on breast cancer incidence and mortality in BRCA mutation carriers, by age at Mastectomy
Breast Cancer Research and Treatment, 2018Co-Authors: Vasily Giannakeas, Steven A. NarodAbstract:Purpose Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of Preventive Mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a Preventive Mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women. Methods The age-specific annual risks of developing breast cancer were used to estimate the actuarial risk of developing breast cancer by age 80 for women with a BRCA1 or BRCA2 mutation. The probability of developing breast cancer before age 80 was then modified to include competing causes of death, including from ovarian cancer. The mortality rate from breast cancer after a diagnosis of breast cancer was set at 2% annually for the first 10 years and then 1% annually for years ten to twenty. The incidence rate and mortality rate from ovarian cancer were based on published literature. We assumed that Preventive Mastectomy was associated with complete protection against subsequent breast cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) until age 80, according to the age at Mastectomy. Results The actuarial risk of developing breast cancer until age 80 was estimated to be 70.8%. The actual risk (incorporating competing risks) was 64.0%. The probability of being alive at age 80 by having a Mastectomy at age 25 increased by 8.7% (from 42.7 to 51.3%). The estimated benefit declined with age at Mastectomy; for surgery done at age 50 the improvement in survival to age 80 was much more modest (2.8% at age 80, from 42.7 to 45.5%). Conclusions Among BRCA mutation carriers, the mortality benefit of Preventive Mastectomy at age 25 is substantial, but the expected benefit declines rapidly with increasing age at surgery.
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The expected benefit of Preventive Mastectomy on breast cancer incidence and mortality in BRCA mutation carriers, by age at Mastectomy.
Breast cancer research and treatment, 2017Co-Authors: Vasily Giannakeas, Steven A. NarodAbstract:Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of Preventive Mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a Preventive Mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women. The age-specific annual risks of developing breast cancer were used to estimate the actuarial risk of developing breast cancer by age 80 for women with a BRCA1 or BRCA2 mutation. The probability of developing breast cancer before age 80 was then modified to include competing causes of death, including from ovarian cancer. The mortality rate from breast cancer after a diagnosis of breast cancer was set at 2% annually for the first 10 years and then 1% annually for years ten to twenty. The incidence rate and mortality rate from ovarian cancer were based on published literature. We assumed that Preventive Mastectomy was associated with complete protection against subsequent breast cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) until age 80, according to the age at Mastectomy. The actuarial risk of developing breast cancer until age 80 was estimated to be 70.8%. The actual risk (incorporating competing risks) was 64.0%. The probability of being alive at age 80 by having a Mastectomy at age 25 increased by 8.7% (from 42.7 to 51.3%). The estimated benefit declined with age at Mastectomy; for surgery done at age 50 the improvement in survival to age 80 was much more modest (2.8% at age 80, from 42.7 to 45.5%). Among BRCA mutation carriers, the mortality benefit of Preventive Mastectomy at age 25 is substantial, but the expected benefit declines rapidly with increasing age at surgery.
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Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is Preventive Mastectomy warranted?
Gynecologic oncology, 2017Co-Authors: Jacob Mcgee, Jan Lubinski, Vasily Giannakeas, Beth Y. Karlan, Jacek Gronwald, Barry P. Rosen, John R. Mclaughlin, Harvey A. Risch, Ping Sun, William D. FoulkesAbstract:Abstract Objective Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from Preventive Mastectomy or from MRI screening. Methods First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with Mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of Mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality. Results Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with Mastectomy. Greater improvements in survival with MRI or Mastectomy were observed for women who had already survived 10years after ovarian cancer, and for women with stage I or II ovarian cancer. Conclusions Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither Preventive Mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer.
Verena Sigl - One of the best experts on this subject based on the ideXlab platform.
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rankl rank from bone loss to the prevention of breast cancer
Open Biology, 2016Co-Authors: Verena Sigl, Laundette P Jones, Josef M PenningerAbstract:RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the Preventive strategy for BRCA1-mutation carriers includes Preventive Mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible Preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer.
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RANKL/RANK: from bone loss to the prevention of breast cancer
Open biology, 2016Co-Authors: Verena Sigl, Laundette P Jones, Josef M PenningerAbstract:RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the Preventive strategy for BRCA1-mutation carriers includes Preventive Mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible Preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer.