Commentary: MRI Surveillance and Risk Factors in Breast Cancer, April 2024

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Women with pathogenic BRCA1/2 mutations are presented options of risk-reducing surgery or enhanced surveillance to address their elevated lifetime risk for breast cancer. In regard to breast cancer screening for these women, guidelines recommend annual mammography and breast MRI for those aged 30-75 years; for younger women (age 25-29 years), annual MRI or an individualized schedule on the basis of family history if a breast cancer diagnosis before age 30 is present.^[1] Prior studies have highlighted the role of screening MRI in "downstaging," meaning MRI screening detected breast cancers at an earlier stage vs those identified with mammography.^[2] As with any screening tool, it is essential to demonstrate the effect of MRI surveillance on mortality for women with BRCA mutations. A cohort study that included 2488 women (age ≥ 30 years) with a BRCA1 (n = 2004) or BRCA2 (n = 484) mutation compared breast cancer mortality rates among those women who participated in MRI screening with those who did not (Lubinski et al). After a median follow-up of 9.2 years, 344 women (13.8%) developed breast cancer, and 35 (1.4%) died from breast cancer. There was an 80% reduction in breast cancer mortality among BRCA1 mutation carriers who participated in MRI surveillance vs those who did not (age-adjusted hazard ratio [HR] 0.20; 95% CI 0.10-0.43; P < .001), but this was not observed for women with BRCA2 mutations (age-adjusted HR 0.87; 95% CI 0.10-17.25; P = .93). At 20 years, the breast cancer mortality rate was 3.2% in the MRI surveillance group compared with 14.9% in the group who did not undergo surveillance. A separate cohort study from Ontario, Canada, including 489 women with BRCA1/2 pathogenic mutations found a 2.0% rate of breast cancer-related mortality at 20 years after the first MRI screening.^[3] These data support an intensified surveillance schedule for BRCA mutation carriers, with a need for further research and insight in the BRCA2 population.

A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.^[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.

Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.^[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to a higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further understand the differences within this subtype itself.

Additional References

National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source
Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): A multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X Source
Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin Roesch, MD

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Erin Roesch, MD

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals, so you don't have to!

Women with pathogenic BRCA1/2 mutations are presented options of risk-reducing surgery or enhanced surveillance to address their elevated lifetime risk for breast cancer. In regard to breast cancer screening for these women, guidelines recommend annual mammography and breast MRI for those aged 30-75 years; for younger women (age 25-29 years), annual MRI or an individualized schedule on the basis of family history if a breast cancer diagnosis before age 30 is present.^[1] Prior studies have highlighted the role of screening MRI in "downstaging," meaning MRI screening detected breast cancers at an earlier stage vs those identified with mammography.^[2] As with any screening tool, it is essential to demonstrate the effect of MRI surveillance on mortality for women with BRCA mutations. A cohort study that included 2488 women (age ≥ 30 years) with a BRCA1 (n = 2004) or BRCA2 (n = 484) mutation compared breast cancer mortality rates among those women who participated in MRI screening with those who did not (Lubinski et al). After a median follow-up of 9.2 years, 344 women (13.8%) developed breast cancer, and 35 (1.4%) died from breast cancer. There was an 80% reduction in breast cancer mortality among BRCA1 mutation carriers who participated in MRI surveillance vs those who did not (age-adjusted hazard ratio [HR] 0.20; 95% CI 0.10-0.43; P < .001), but this was not observed for women with BRCA2 mutations (age-adjusted HR 0.87; 95% CI 0.10-17.25; P = .93). At 20 years, the breast cancer mortality rate was 3.2% in the MRI surveillance group compared with 14.9% in the group who did not undergo surveillance. A separate cohort study from Ontario, Canada, including 489 women with BRCA1/2 pathogenic mutations found a 2.0% rate of breast cancer-related mortality at 20 years after the first MRI screening.^[3] These data support an intensified surveillance schedule for BRCA mutation carriers, with a need for further research and insight in the BRCA2 population.

A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.^[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.

Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.^[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to a higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further understand the differences within this subtype itself.

Additional References

National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source
Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): A multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X Source
Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source

Women with pathogenic BRCA1/2 mutations are presented options of risk-reducing surgery or enhanced surveillance to address their elevated lifetime risk for breast cancer. In regard to breast cancer screening for these women, guidelines recommend annual mammography and breast MRI for those aged 30-75 years; for younger women (age 25-29 years), annual MRI or an individualized schedule on the basis of family history if a breast cancer diagnosis before age 30 is present.^[1] Prior studies have highlighted the role of screening MRI in "downstaging," meaning MRI screening detected breast cancers at an earlier stage vs those identified with mammography.^[2] As with any screening tool, it is essential to demonstrate the effect of MRI surveillance on mortality for women with BRCA mutations. A cohort study that included 2488 women (age ≥ 30 years) with a BRCA1 (n = 2004) or BRCA2 (n = 484) mutation compared breast cancer mortality rates among those women who participated in MRI screening with those who did not (Lubinski et al). After a median follow-up of 9.2 years, 344 women (13.8%) developed breast cancer, and 35 (1.4%) died from breast cancer. There was an 80% reduction in breast cancer mortality among BRCA1 mutation carriers who participated in MRI surveillance vs those who did not (age-adjusted hazard ratio [HR] 0.20; 95% CI 0.10-0.43; P < .001), but this was not observed for women with BRCA2 mutations (age-adjusted HR 0.87; 95% CI 0.10-17.25; P = .93). At 20 years, the breast cancer mortality rate was 3.2% in the MRI surveillance group compared with 14.9% in the group who did not undergo surveillance. A separate cohort study from Ontario, Canada, including 489 women with BRCA1/2 pathogenic mutations found a 2.0% rate of breast cancer-related mortality at 20 years after the first MRI screening.^[3] These data support an intensified surveillance schedule for BRCA mutation carriers, with a need for further research and insight in the BRCA2 population.

A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.^[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.

Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.^[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to a higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further understand the differences within this subtype itself.

Additional References

National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source
Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): A multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X Source
Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source

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