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Breast cancer in pregnancy: Recommendations of an international consensus meeting
Breast cancer in pregnancy: Recommendations of an international consensus meeting Frdric A, Sarah D, Kristel VC, et al (Katholieke Universiteit Leuven, Belgium; et al) Eur J Cancer 46:3158-3168, 2010
Purpose.—To provide guidance for clinicians about the diagnosis, staging and treatment of breast cancer occurring during an otherwise uncomplicated pregnancy. Methods.—An international expert Panel convened to address a series of questions identified by a literature review and personal experience. Issues relating to the diagnosis and management of breast cancer after delivery were outside the scope. Results.—There is a paucity of large and/or randomized studies. Based on cohort studies, case series and case reports, the recommendations represent the best available evidence, albeit of a lower grade than is optimal. Recommendations.—In most circumstances, serious consideration should be given to the option of treating breast cancer whilst continuing with the pregnancy. Each woman should ideally be referred to a centre with sufficient expertise, given a clear explanation of treatment options. Most diagnostic and staging examinations can be performed adequately and safely during pregnancy. Treatment should however be adapted to the clinical presentation and the trimester of the pregnancy: surgery can be performed during all trimesters of pregnancy; radiotherapy can be considered during the first and second trimester but should be postponed during the third trimester; and
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standard chemotherapies can be used during the second and third trimester. Since neonatal morbidity mainly appears to be related to prematurity, delivery should not be induced before 37 weeks, if at all possible. Conclusions.—The treatment of breast cancer in pregnancy should be executed by experienced specialists in a multidisciplinary setting and should adhere as closely as possible to standard protocols. A multidisciplinary panel of European expert physicians convened to give consensus opinions on the treatment of breast cancer occurring concomitantly with pregnancy. Although interest is increasing as more women are delaying childbearing, the nature of this occurrence cannot be studied in a prospectively controlled manner. Therefore, data and guidelines come mostly from case reports, series, and case-control studies. This review article describes some of the basic principles of treating women with cancer during pregnancy. First, a multidisciplinary approach should be taken, with surgeons, pathologists, medical oncologists, radiologists, and obstetricians, all communicating effectively during the treatment of the pregnant patient with breast cancer. Second, treatment, including surgery and chemotherapy, during pregnancy can be effective and safe. Denying treatment may put the patients at risk for continued tumor growth. Chemotherapy should be given only after the first trimester to avoid an increased risk of birth defects. Most data reflect anthracycline-containing regimens. Methotrexate should be avoided. This panel discussed the limited use of trastuzumab during pregnancy in Europe; however, given
Breast Diseases: A Year BookÒ Quarterly Vol 22 No 2 2011
these same toxicity reports, the US Food and Drug Administration has now classified trastuzumab as a Pregnancy Category D agent and recommended against its use during pregnancy in the United States.1 Tamoxifen therapy should be delayed until after delivery because of the risk of birth defects. Third, the data regarding long-term health concerns in children exposed to chemotherapy in utero are scarce, and continued collaboration among cancer centers to provide that data and potentially prospectively register these children should be encouraged. In contrast to findings presented in this review, our cancer center delays radiation therapy until after delivery, which is often not difficult to do with pre- or postoperative chemotherapy. We have seen no significant difference in complications from breast-conserving surgeries in our pregnant patients. Also, there is emerging data on the safety of taxanes given during pregnancy, and 40 cases are currently described in the literature2; indeed, the addition of taxanes may soon be considered standard chemotherapy during pregnancy as reports continue to be published. Overall, this is a very thorough review of the literature, even though several subjective conclusions were reached in the absence of available data. J. K. Litton, MD
References 1. U.S. Food and Drug Administration. Herceptin (trastuzumab) Intravenous Infusion: Safety Information. http:// www.fda.gov/Safety/MedWatch/ SafetyInformation/Safety-Related DrugLabelingChanges/ucm106665. htm. Accessed March 22, 2011.
2. Mir O, Berveiller P, Goffinet F, et al. Taxanes for breast cancer during
Race and Ethnicity and Breast Cancer Outcomes in an Underinsured Population Komenaka IK, Martinez ME, Pennington RE Jr, et al (Indiana Univ, Indianapolis; Univ of Arizona, Tucson) J Natl Cancer Inst 102:1178-1187, 2010
Background.—The disparity in breast cancer mortality between African American women and non-Hispanic white women has been the subject of increased scrutiny. Few studies have addressed these differences in the setting of equal access to health care. We compared the breast cancer outcomes of underinsured African American and non-Hispanic white patients who were treated at a single institution. Methods.—We conducted a retrospective review of medical records for breast cancer patients who were treated at Wishard Memorial Hospital from January 1, 1997, to February 28, 2006. A total of 574 patients (259 nonHispanic whites and 315 African Americans) were evaluated. A Cox proportional hazards regression analysis for competing risks was performed. All statistical tests were two-sided. Results.—Sociodemographic characteristics were similar in the two groups, and both racial groups were equally unlikely to have undergone screening mammography during the 2 years before diagnosis. Most (84%) of the patients were underinsured. The median time from diagnosis to operation, receipt of adequate surgery, and
pregnancy: a systematic review. Ann Oncol. 2010;21:425-426.
use of all types of adjuvant therapy were similar in the two groups. Median follow-up was 80.3 months for nonHispanic whites and 77.9 months for African Americans. After accounting for the effect of comorbidities, African American race was statistically significantly associated with breast cancer– specific mortality (African Americans vs non-Hispanic whites: 26.0% vs 17.5%, P ¼.028; hazard ratio [HR] of death ¼ 1.64, 95% confidence interval [CI] ¼ 1.06 to 2.55). Adjustment for age at diagnosis, clinical stage, and hormone receptor status attenuated the effect, and the effect of race on breast cancer–specific survival was no longer statistically significant (HR of death from breast cancer ¼ 1.43, 95% CI ¼ 0.89 to 2.30). After adjustment for sociodemographic factors, the hazard ratio for race was further attenuated (HR ¼ 1.26; 95% CI ¼ 0.79 to 2.00). Conclusions.—In this underinsured population, African American patients had poorer breast cancer–specific survival than non-Hispanic white patients. After adjustment for clinical and sociodemographic factors, the effect of race on survival was no longer statistically significant. Numerous prior studies have noted significantly worse breast cancer– specific survival in African American women diagnosed with breast cancer compared with their white counterparts. This study by Komenaka and colleagues supports an emerging body of evidence that identifies specific
socioeconomic and clinical factors that help explain survival differences by race. It is unique in its study design by focusing on a socioeconomically disadvantaged group of patients, the underinsured and uninsured. In this group, differences in insurance status and treatment history were minimal. Results from this study, together with other evidence from better-insured populations, provide accumulating data that point to the need for multimodality interventions to eliminate racial disparities in breast cancer– specific survival. First, evidence suggests that the promotion of breast cancer screening may be an important target, given the consistent finding that African American patients are diagnosed with breast cancer at later stages. Second, an important current research priority includes developing strategies to improve therapies and outcomes for patients diagnosed with more advanced breast cancer and estrogen receptor–negative breast cancer. Third and finally, the value of policy measures to help provide coverage for underinsured and uninsured patients, as well as to promote standards for the highest-quality treatment strategies, cannot be ignored as an important component of interventions to eliminate racial disparities in breast cancer. G. L. Smith, MD
Breast Diseases: A Year BookÒ Quarterly Vol 22 No 2 2011
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Purpose.—To provide guidance for clinicians about the diagnosis, staging and treatment of breast cancer occurring during an otherwise uncomplicated pregnancy. Methods.—An international expert Panel convened to address a series of questions identified by a literature review and personal experience. Issues relating to the diagnosis and management of breast cancer after delivery were outside the scope. Results.—There is a paucity of large and/or randomized studies. Based on cohort studies, case series and case reports, the recommendations represent the best available evidence, albeit of a lower grade than is optimal. Recommendations.—In most circumstances, serious consideration should be given to the option of treating breast cancer whilst continuing with the pregnancy. Each woman should ideally be referred to a centre with sufficient expertise, given a clear explanation of treatment options. Most diagnostic and staging examinations can be performed adequately and safely during pregnancy. Treatment should however be adapted to the clinical presentation and the trimester of the pregnancy: surgery can be performed during all trimesters of pregnancy; radiotherapy can be considered during the first and second trimester but should be postponed during the third trimester; and
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standard chemotherapies can be used during the second and third trimester. Since neonatal morbidity mainly appears to be related to prematurity, delivery should not be induced before 37 weeks, if at all possible. Conclusions.—The treatment of breast cancer in pregnancy should be executed by experienced specialists in a multidisciplinary setting and should adhere as closely as possible to standard protocols. A multidisciplinary panel of European expert physicians convened to give consensus opinions on the treatment of breast cancer occurring concomitantly with pregnancy. Although interest is increasing as more women are delaying childbearing, the nature of this occurrence cannot be studied in a prospectively controlled manner. Therefore, data and guidelines come mostly from case reports, series, and case-control studies. This review article describes some of the basic principles of treating women with cancer during pregnancy. First, a multidisciplinary approach should be taken, with surgeons, pathologists, medical oncologists, radiologists, and obstetricians, all communicating effectively during the treatment of the pregnant patient with breast cancer. Second, treatment, including surgery and chemotherapy, during pregnancy can be effective and safe. Denying treatment may put the patients at risk for continued tumor growth. Chemotherapy should be given only after the first trimester to avoid an increased risk of birth defects. Most data reflect anthracycline-containing regimens. Methotrexate should be avoided. This panel discussed the limited use of trastuzumab during pregnancy in Europe; however, given
Breast Diseases: A Year BookÒ Quarterly Vol 22 No 2 2011
these same toxicity reports, the US Food and Drug Administration has now classified trastuzumab as a Pregnancy Category D agent and recommended against its use during pregnancy in the United States.1 Tamoxifen therapy should be delayed until after delivery because of the risk of birth defects. Third, the data regarding long-term health concerns in children exposed to chemotherapy in utero are scarce, and continued collaboration among cancer centers to provide that data and potentially prospectively register these children should be encouraged. In contrast to findings presented in this review, our cancer center delays radiation therapy until after delivery, which is often not difficult to do with pre- or postoperative chemotherapy. We have seen no significant difference in complications from breast-conserving surgeries in our pregnant patients. Also, there is emerging data on the safety of taxanes given during pregnancy, and 40 cases are currently described in the literature2; indeed, the addition of taxanes may soon be considered standard chemotherapy during pregnancy as reports continue to be published. Overall, this is a very thorough review of the literature, even though several subjective conclusions were reached in the absence of available data. J. K. Litton, MD
References 1. U.S. Food and Drug Administration. Herceptin (trastuzumab) Intravenous Infusion: Safety Information. http:// www.fda.gov/Safety/MedWatch/ SafetyInformation/Safety-Related DrugLabelingChanges/ucm106665. htm. Accessed March 22, 2011.
2. Mir O, Berveiller P, Goffinet F, et al. Taxanes for breast cancer during
Race and Ethnicity and Breast Cancer Outcomes in an Underinsured Population Komenaka IK, Martinez ME, Pennington RE Jr, et al (Indiana Univ, Indianapolis; Univ of Arizona, Tucson) J Natl Cancer Inst 102:1178-1187, 2010
Background.—The disparity in breast cancer mortality between African American women and non-Hispanic white women has been the subject of increased scrutiny. Few studies have addressed these differences in the setting of equal access to health care. We compared the breast cancer outcomes of underinsured African American and non-Hispanic white patients who were treated at a single institution. Methods.—We conducted a retrospective review of medical records for breast cancer patients who were treated at Wishard Memorial Hospital from January 1, 1997, to February 28, 2006. A total of 574 patients (259 nonHispanic whites and 315 African Americans) were evaluated. A Cox proportional hazards regression analysis for competing risks was performed. All statistical tests were two-sided. Results.—Sociodemographic characteristics were similar in the two groups, and both racial groups were equally unlikely to have undergone screening mammography during the 2 years before diagnosis. Most (84%) of the patients were underinsured. The median time from diagnosis to operation, receipt of adequate surgery, and
pregnancy: a systematic review. Ann Oncol. 2010;21:425-426.
use of all types of adjuvant therapy were similar in the two groups. Median follow-up was 80.3 months for nonHispanic whites and 77.9 months for African Americans. After accounting for the effect of comorbidities, African American race was statistically significantly associated with breast cancer– specific mortality (African Americans vs non-Hispanic whites: 26.0% vs 17.5%, P ¼.028; hazard ratio [HR] of death ¼ 1.64, 95% confidence interval [CI] ¼ 1.06 to 2.55). Adjustment for age at diagnosis, clinical stage, and hormone receptor status attenuated the effect, and the effect of race on breast cancer–specific survival was no longer statistically significant (HR of death from breast cancer ¼ 1.43, 95% CI ¼ 0.89 to 2.30). After adjustment for sociodemographic factors, the hazard ratio for race was further attenuated (HR ¼ 1.26; 95% CI ¼ 0.79 to 2.00). Conclusions.—In this underinsured population, African American patients had poorer breast cancer–specific survival than non-Hispanic white patients. After adjustment for clinical and sociodemographic factors, the effect of race on survival was no longer statistically significant. Numerous prior studies have noted significantly worse breast cancer– specific survival in African American women diagnosed with breast cancer compared with their white counterparts. This study by Komenaka and colleagues supports an emerging body of evidence that identifies specific
socioeconomic and clinical factors that help explain survival differences by race. It is unique in its study design by focusing on a socioeconomically disadvantaged group of patients, the underinsured and uninsured. In this group, differences in insurance status and treatment history were minimal. Results from this study, together with other evidence from better-insured populations, provide accumulating data that point to the need for multimodality interventions to eliminate racial disparities in breast cancer– specific survival. First, evidence suggests that the promotion of breast cancer screening may be an important target, given the consistent finding that African American patients are diagnosed with breast cancer at later stages. Second, an important current research priority includes developing strategies to improve therapies and outcomes for patients diagnosed with more advanced breast cancer and estrogen receptor–negative breast cancer. Third and finally, the value of policy measures to help provide coverage for underinsured and uninsured patients, as well as to promote standards for the highest-quality treatment strategies, cannot be ignored as an important component of interventions to eliminate racial disparities in breast cancer. G. L. Smith, MD
Breast Diseases: A Year BookÒ Quarterly Vol 22 No 2 2011
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