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Emerging Data on Challenges in Gynecologic Care of Premenopausal Women With Breast Cancer

      To the Editor: In the March 2011 issue of Mayo Clinic Proceedings, we published a review article entitled “Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer” that discussed pharmacologic options for managing vasomotor symptoms. Much of our article focused on selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors.
      • Bakkum-Gamez JN
      • Laughlin SK
      • Jensen JR
      • Akogyeram CO
      • Pruthi S
      Challenges in the gynecologic care of premenopausal women with breast cancer.
      Some of the research we referenced reported interactions between tamoxifen and those specific SSRIs that interfere with CYP2D6 enzyme activity (ie, the enzyme responsible for metabolism of tamoxifen to the bioactive form endoxifen), resulting in an increased risk of breast cancer recurrence.
      • Bordeleau L
      • Pritchard K
      • Goodwin P
      • Loprinzi C
      Therapeutic options for the management of hot flashes in breast cancer survivors: an evidence-based review.
      • Goetz MP
      • Knox SK
      • Suman VJ
      • et al.
      The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen.
      However, emerging data from 2 major trials now reveal conflicting findings. The BIG (Breast International Group) 1-98 trial and ATAC (Arimidex or Tamoxifen Alone or in Combination) trial did not find an association between variations of baseline CYP2D6 levels, or the concomitant use of medications that can inhibit CYP2D6, on tamoxifen efficacy or influence on breast cancer outcomes.

      Rae JM, Drury S, Hayes DF, et al. Lack of correlation between gene variants in tamoxifen metabolizing enzymes with primary endpoints in the ATAC trial [abstract S1-7]. Abstract presented at: 33rd Annual San Antonio Breast Cancer Symposium; San Antonio, TX; December 8-12, 2010. http://www.abstracts2view.com/sabcs10/view.php?nu=SABCS10L_1093. Accessed March 3, 2011.

      • Leyland-Jones B
      • Regan MM
      • Bouzyk M
      • et al.
      Outcome according to CYP 2D6 genotype among postmenopausal women with endocrine-responsive early invasive breast cancer randomized in the BIG 1-98 Trial [abstract S1-8]. Abstract presented at: 33rd Annual San Antonio Breast Cancer Symposium; San Antonio, TX; December 8-12, 2010.
      It is noteworthy that both analyses were retrospective, and study limitations included a lack of information about concomitant use of medications that reduce the severity of hot flashes. Prospective trials are under way to assess the extent to which variation in tamoxifen pharmacokinetics affects patient outcomes.
      • Eastern Cooperative Oncology Group
      ECOG active protocols Web site. ECOG protocols active as of 03/03/11.
      Until further data are available, physicians should continue to use caution with regard to the use of potent CYP2D6 inhibitors in women receiving tamoxifen.

      REFERENCES

        • Bakkum-Gamez JN
        • Laughlin SK
        • Jensen JR
        • Akogyeram CO
        • Pruthi S
        Challenges in the gynecologic care of premenopausal women with breast cancer.
        Mayo Clin Proc. 2011; 86: 229-240
        • Bordeleau L
        • Pritchard K
        • Goodwin P
        • Loprinzi C
        Therapeutic options for the management of hot flashes in breast cancer survivors: an evidence-based review.
        Clin Ther. 2007; 29: 230-241
        • Goetz MP
        • Knox SK
        • Suman VJ
        • et al.
        The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen.
        Breast Cancer Res Treat. 2007; 101: 113-121
      1. Rae JM, Drury S, Hayes DF, et al. Lack of correlation between gene variants in tamoxifen metabolizing enzymes with primary endpoints in the ATAC trial [abstract S1-7]. Abstract presented at: 33rd Annual San Antonio Breast Cancer Symposium; San Antonio, TX; December 8-12, 2010. http://www.abstracts2view.com/sabcs10/view.php?nu=SABCS10L_1093. Accessed March 3, 2011.

        • Leyland-Jones B
        • Regan MM
        • Bouzyk M
        • et al.
        Outcome according to CYP 2D6 genotype among postmenopausal women with endocrine-responsive early invasive breast cancer randomized in the BIG 1-98 Trial [abstract S1-8]. Abstract presented at: 33rd Annual San Antonio Breast Cancer Symposium; San Antonio, TX; December 8-12, 2010.
        (Accessed March 3, 2011.)
        • Eastern Cooperative Oncology Group
        ECOG active protocols Web site. ECOG protocols active as of 03/03/11.
        (Accessed March 3, 2011.)