With not enough progress on breast cancer, patients and doctors alike are eager for the next best thing. Today at SABCS there was a lot of trumpeting that the next best thing is here! It involves Tamoxifen. And although I’m as ready as anyone for a breakthrough, we know from experience we have to look beyond the headlines for the real story on “groundbreaking” breast cancer news.
Tamoxifen is an anti-estrogen drug given to women with hormone sensitive breast cancer to prevent spread and recurrence. Used widely for more than two decades, tamoxifen is relatively cheap and has been available in generic form for 10 years. Tamoxifen remains the standard treatment for approximately two-thirds of breast cancer patients with estrogen sensitive breast cancer.
Current protocols recommend five years of tamoxifen which has been shown to reduce death from breast cancer by approximately one-third. Earlier studies in the 1990s suggested that extending tamoxifen beyond five years not only increased toxicity but also produced worse outcomes for women on ten years of tamoxifen.
Today the results from the ATLAS study were reported. ATLAS—which stands for Adjuvant Tamoxifen: Longer Against Shorter—is a worldwide collaborative trial started in 1996. Nearly 7,000 women (6846) women with hormone sensitive (ER+) breast cancer were enrolled in a dozen countries. Just over half of the women (54%) had no lymph node involvement. This large study looks for small differences in the risk of recurrence and death for women who take tamoxifen for five years versus ten years.
Tamoxifen is unusual in that the beneficial effects persist for a number of years after stopping treatment; such that five years of tamoxifen brings an extended benefit for an additional five years. In order to evaluate ten years of tamoxifen, any potential benefit of this longer treatment must be compared to the known extended benefit of five additional years of benefit from five years of treatment.
The ATLAS results show, and the media widely trumpeted, that doubling the length of time women take tamoxifen does reduce the risk of recurrence and death. Just over one in five women who took the longer ten-year course of tamoxifen experienced a recurrence (21.4%) compared to one in four (25.1%) women who took the current five year standard. This amounts to an absolute difference of 3.7%. More importantly, 12.2% of women in the ten year arm died from breast cancer compared to 15% of women in the five year arm, an absolute difference of 2.8%. The researchers noted that the benefit was mainly seen after ten years, with relatively little effect in years 5-9 when the two arms of the study (five vs. ten years) saw similar outcomes.
The toxicity of tamoxifen is well known. Not surprisingly, doubling the duration of tamoxifen also doubles the risk of endometrial cancer (from 1.6% to 3.1%) and death from endometrial cancer (from 0.2% to 0.4%). Additionally there were more blood clots although not more fatality as a result of the blood clots. The presenter confidently calculated “there is a 30x benefit versus the risks” of extending tamoxifen.
Yet as many patients and patient advocates know, the risk and benefit that matter to women don’t always show up on presentation slides at conferences. Quality of life issues factor in heavily to women’s decision to continue treatment or not. Approximately 30% of women discontinued tamoxifen treatment early because of side effects and quality of life issues. We know that some patients are so miserable on tamoxifen that even a 3% reduction of disease or death is not enough to tip the balance for women. One doctor on the panel discussion that evening acknowledged: “It’s all I can do to get some patients to take [tamoxifen] for five years. If life is miserable, you have to weigh benefits and risks.”
Despite what you read in the media, some patients and doctors attending the conference are not so sure that more is, in fact, better when it comes to tamoxifen. The question is: does the relatively modest benefit warrant the additional treatment? And if so, which women may choose to extend tamoxifen?
Several doctors in an evening discussion insisted that the data do not necessarily make the case that everyone should take tamoxifen for ten years. Recognizing the significant quality of life issues from tamoxifen, the question is: what is the level of risk that would warrant a woman signing up for five more years of tamoxifen? While ER+ breast cancers tend to have better prognosis, younger women are at higher risk and (knowing they are ineligible for aromatase inhibitors) perhaps they might be recommended additional years of tamoxifen. Furthermore, women who can’t tolerate the side effects of aromatase inhibitors may consider extending tamoxifen treatment.
I’m eager for the next best thing, and I’m still waiting.
For more commentary on this new study from a patient advocate perspective, check out this post from fellow advocate and BCAction member AnneMarie Ciccarella.