Tamoxifen-induced Hot Flushes: The Switch is On
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: In an open-label cross-over trial of an aromatase inhibitor in early stage post-menopausal breast cancer, patients who had become intolerant of the menopausal symptoms associated with Tamoxifen improved in this regard by switching to an aromatase inhibitor (AI). After six weeks and three months of AI treatment, most (but not all) women chose to remain on AI rather than switch back to Tam. For some, arthralgia or other symptoms associated with AI treatment prompted the switch back to Tam, and a smaller percentage (12%) found both drugs to be intolerable, and discontinued treatment on the study completely.
Source: Thomas R, et al. Br. J Cancer. 2008;98:1494-1499.
Endocrine interventions have become stan- dard therapy for post menopausal women with breast cancer. Several large trials have demonstrated improved disease free survival with aromatase inhibitors (AI) when compared with tamoxifen (Tam), yet for women with favorable prognostic indicators the advantage of AI over Tam is very small. Certain subgroups have been identified who are more likely to benefit from AI over Tam, including those with negative prognostic factors, but also patient-related factors, such as a history of thromboembolic disease or uterine cancer. Alternatively, because AIs are associated with arthralgias and vaginal dryness, Tam might be considered a more reasonable initial treatment for some.
A common complaint among Tam-treated patients is hot flushes and other menopausal symptoms. The current study was designed to determine if switching from Tam to an AI (either letrozole or exemestane) in women who were intolerant of Tam because of menopausal symptoms would result in a reduction in those symptoms and improved quality of life.
To accomplish this, Thomas and colleagues in the UK performed an open-label, prospective, crossover study involving 184 post-menopausal women experiencing hot flushes on adjuvant Tam. Six weeks after switching to an AI, the primary end point hot flush score improved by 47.3% (P < 0.001) compared to those reported on Tam. The mean mood rating scale (MRS) score (a self-reported index of mood that employs six visual analogue scales1) improved by 9.7% (P = 0.01). Quality of life, as assessed by the Functional Assessment of Cancer Therapy (FACT) instrument including specific scales for breast cancer and endocrine symptoms2 improved from a score of 134.2 (95% CI ± 2.96) to 143.5 (95% CI ± 2.96; P < 0.001), and the endocrine subscale improved by 9.8% from 51.73 (95% CI ± 1.38) to 57.34 (CI ± 1.38, P < 0.001). At six weeks, significantly more women chose to remain on an AI: 133 (72%), vs 40 (22%) who chose to return to Tam (P < 0.001). At three months, 107 (58%) preferred to remain on an AI, 55 (30%) returned to Tam, and 22 (12%) withdrew. Arthralgia had occurred in 47% on AI and 30% on TAM (P < 0.001) by three months of treatment. These data provide a measure of likely success by reducing TAM-associated menopausal symptoms by switching to AI. The value of having patients involved in the choice (ie, to switch back or not switch back to TAM) was considered favorably by both patients and investigators.
Commentary
Clinical oncologists strive to practice evidence-based medicine, but are oftentimes confronted with issues for which there are no solid data. Although there are a number of studies in which the sequence of Tamoxifen followed by aromatase inhibitor has proven both safe and effective in the adjuvant setting,3,4 it is usually done after sustained Tam treatment and in an effort to extend disease-free and overall survival. The current report provides evidence that the switch might also be useful for quality of life issues. Menopausal symptoms are not uncommon with Tam treatment, and for some they are intolerable. Pharmacological approaches include progestogens, clonidine and venlafaxine but these are of variable success and each has its own set of possible adverse effects.5,6 In this series of 184 postmenopausal breast cancer patients who were not tolerating Tam because of hot flushes or other menopausal symptoms, there was significant improvement in these symptoms, and other measures of quality of life after switching to either letrozole or exemestane. These drugs, although not associated with menopausal symptoms to the extent of Tam, are associated with arthralgia and other nagging concerns, such as vaginal dryness. Thus, at six weeks, or three months after the switch from Tam to AI, it is not surprising that some patients found these AI-associated symptoms to be of greater consequence than the Tam-associated menopausal symptoms, and switched back.
Practitioners may use this information and engage patients on a case-by-case basis, discussing the pros and cons of switching from Tam to an AI for the purpose of alleviating hot flushes or other menopausal symptoms. There is now some data, albeit not from a randomized trial, on which the likelihood of achieving a satisfactory outcome may be gauged.
References
1. Walker LG, et al. Psychological, clinical and pathological effects of relaxation training and guided imagery during primary chemotherapy. Br J Cancer. 1999;80(1-2):262-268.
2. Cella D. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol. 1997;34(3 Suppl 2):13-19.
3. Boccardo F, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol. 2005;23(22):5138-547.
4. Coombes RC, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350(11):1081-1092.
5. Carpenter JS, et al. Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life. Cancer. 1998;82(9):1682-1691.
6. Loibl S, et all. Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients--a double-blind, randomized study. Ann Oncol. 2007;18(4):689-693.
In an open-label cross-over trial of an aromatase inhibitor in early stage post-menopausal breast cancer, patients who had become intolerant of the menopausal symptoms associated with Tamoxifen improved in this regard by switching to an aromatase inhibitor (AI).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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