Updated Breast Cancer Guidelines Increase Duration of Preventive Tamoxifen Treatment From 5 Years to 10 Years

Results from 2 large, long-term clinical trials show benefits of extended-duration treatment with tamoxifen, resulting in an update to treatment guidelines.

A clinical practice guideline update published on May 27, 2014 in the Journal of Clinical Oncology by Burstein and colleagues clarifies the role of long-term treatment with tamoxifen in patients with certain types of breast cancer that contain hormone receptors.¹

The majority of breast cancers (65% to 75%) contain estrogen receptors, and among breast cancers that contain estrogen receptors, almost two-thirds (65%) also contain progesterone receptors. The presence of these receptors increases the likelihood that tumors will grow when estrogen and progesterone are plentiful in the body. By diminishing exposure to hormones through long-term use of tamoxifen, breast cancer may be less likely to recur.^1,2

A previous update to guidelines issued in 2010 recommended the use of tamoxifen for no more than 5 years in women attempting to reduce the risk of developing breast cancer. At that time, studies showed equivocal results in prevention of breast cancer with use of tamoxifen beyond the 5-year mark.³

Although survival outcomes were mixed in 3-decades-old smaller trials, 2 new, larger studies evaluated the efficacy of tamoxifen beyond the 5-year mark. These trials, the 12,894-patent ATLAS trial and the 6953-patient aTTom trial, showed a lower risk of recurrence with 10 years of therapy than with 5 years of therapy.¹

In the ATLAS trial, the rate of recurrence was significantly lower in women who received 10 or more years of therapy than in women who received 5 to 9 years of therapy (25.1% vs 21.4%, P = .002; see the Kaplan-Meier curve here).^3,4

The aTTom trial results also showed a statistically significant benefit over shorter-duration therapy in 2 subpopulations of patients: patients who had received 7 to 9 years of therapy and patients who had received 10 to 14 years of therapy (28% with longer-term treatment vs 32% with shorter-term treatment, amounting to a 15% reduction in the risk of recurrence; P = 0.003). However, in the aTTom trial, durations of therapy exceeding 10 to 14 years did not lead to a survival benefit, suggesting that further extensions of the duration of treatment with tamoxifen are unlikely.^3-5

Although use of tamoxifen for a duration of 10 years is now recommended for menopausal, pre- or perimenopausal women, or women of unknown menopausal status, the level of evidence for tamoxifen use is slightly stronger (level of evidence: IA) in pre- and perimenopausal women than in postmenopausal women (level of evidence: IIB).³

Recommendations for use of tamoxifen may have changed with the guideline update, but use of an aromatase inhibitor (eg, anastrazole) is still recommended for no more than 5 years. Other options include using tamoxifen for 5 years and then switching to 5 years of an anastrazole inhibitor. Conversely, in patients who have already taken anastrazole for 5 years, use of tamoxifen for an additional 5 years is another treatment option.³

Use of tamoxifen may increase the risk of endometrial cancer and may increase the risk of VTE and pulmonary embolism due to its partial agonistic/antagonistic effect on estrogen receptors in different body tissues. Although investigators noted a modest survival improvement with extended therapy and a reduced risk of developing cancer in the opposite-side breast, overall mortality from diseases other than breast cancer was unaffected.^2,3

Investigators analyzed the risk/benefit ratio of extending tamoxifen for 10 years and determined that no new types of adverse events were observed with extended-duration treatment, but noted that the risks of developing menopausal symptoms, and (rarely) VTE and endometrial cancer were still present.³

As noted by investigators, the benefits and risks of therapy must be considered in individual women. Clinicians should take into account the patient's menopausal symptoms, the patient's risk (including family history) of uterine cancer, and the patient's risk of osteoporosis, which can be exacerbated by long-term use of tamoxifen.³

References:

• Burstein HJ, Temin S, Anderson H, et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2014.
• NOLVADEX (tamoxifen citrate) tablets [package insert]. Wilmington, DE: AstraZeneca; 2004.
• Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol.2010;28(23):3784-3796.
• Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805-816.
• Azim HA, Saadeldeen A. Commentary on “aTTom”: long-term effects of continuing adjuvant Tamoxifen to 10 years. Chinese Clinical Oncology. 2014;3(1):7.