By Karuna Jaggar, Executive Director
Some of you who follow me on Twitter know that I live tweet at #SABCS, providing relatively real-time updates and analysis of the research being presented. One of my most “liked” tweets—and the number keeps growing—is this:
The strong response gets at how much women hate taking tamoxifen.
Tamoxifen is the oldest and most common breast cancer treatment and was made more than 50 years ago. It’s cheap (at around $1 a day) and effective. Treatment with tamoxifen is usually a daily pill for five years (and up to 10 years). And even though it can cause endometrial (or uterine) cancer, it is generally considered to be relatively safe—and is, relatively speaking, given the side effects of other breast cancer treatments.
But people hate it. And many people stop taking it before they have completed the full course of treatment. Estimates vary, but an older study found that a third of patients (35.2%) had stopped taking tamoxifen at 3.5 years, despite recommended treatment for a minimum of five years.
The Italian researcher, Dr. DeCensi, who presented the first paper on Thursday morning (GS3-01) noted that even though tamoxifen had been developed 50 years ago, the minimum active dose of tamoxifen isn’t known. That’s shocking and says a lot about how breast cancer research is conducted, with ever escalating treatments piling on top of each other in the hope of gaining incremental benefit.
Based on a small study 15 years ago that showed 5 mg (and even 1 mg) was not inferior to the standard 20 mg per day, the Italian group conducted a randomized placebo controlled phase III trial of low dose tamoxifen for noninvasive conditions called breast intraepithelial neoplasia (which includes ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), and atypical ductal hyperplasia (ADH)). The researchers wanted to know if they could reduce the risk of disease recurrence and new disease with a low dose of tamoxifen (5 mg per day). [Note: because 5 mg pills aren’t available they actually offered a reduced dose of 10mg every other day.]
The study enrolled 500 participants 14 centers in Italy, with DCIS, LCIS, or ADH who had been treated with surgery and, in some cases, radiotherapy. The median age of participants was 54 and just under half were premenopausal. Participants were randomized to receive either low-dose tamoxifen or placebo for three years.
At median follow-up of just over five years, 14 (5.5%) of the 253 patients in the low-dose tamoxifen arm compared to 28 (11.3%) of the 247 patients in the placebo arm had disease recurrence or new disease. While the absolute risk is low, the researchers calculated that low-dose tamoxifen reduced risk by 52 percent. The majority of these recurrences or new disease were noninvasive: just three of the 14 events on low dose tamoxifen were invasive breast cancer compared to 10 of the 28 events on placebo.
There was one death on tamoxifen and two deaths on placebo. There was one case of endometrial cancer on low dose tamoxifen. Overall, the researchers concluded that the rate of endometrial cancer and deep vein thrombosis (DVT) was not different from placebo. But they noted these serious toxicities were 2.5 times lower than 20Mg daily.
There were no significant differences between the two arms in musculoskeletal pain or menopausal symptoms, such as hot flashes, vaginal dryness, and pain during intercourse.
Between 35-40 percent of women in the study stopped taking the treatment: just 64.8 percent and 60.7 percent of patients in the tamoxifen and placebo arms, respectively, completed treatment.
Dr. DeCensi concluded with a beautiful summary of the likelihood of benefit compared to harm. This study found that you would need to treat 22 people to prevent one case of breast cancer. For every 218 women treated, you can anticipate one harm. Therefore, the likelihood of benefit is 10 times that of likelihood of harm, the researcher concluded. Of course, that presumes that the harms and benefits are equal, and that is up to each person to weigh and decide.
For now, the researchers—and lots of patients who are enthusiastic about my tweet—believe this is treatment ready data that can go into practice right away.
Two studies looked at extending aromatase inhibitors beyond five years: the British EBCTCG (Early Breast Cancer Trialists Collaborative Group) (GS3-03) and the Japanese AERAS (Arimidex extended adjuvant randomized study) (GS3-04). Even though both groups of researchers reported some positive findings, as Dr. Laura Esserman said after the EBCTCG presentation: “There’s a difference between clinical significance and statistical significance.” When few women benefit, you need to treat a whole lot of women with extended hormone therapy for just one person to benefit, meaning the need to treat numbers are very high. That’s a calculation that weighs overtreatment for most people against the chance of benefiting one.
As he was wrapping up his presentation, Dr. DeCensi went out of his way to make the point that they are “Committed to fair, equitable and affordable medicine.” Bravo. And we can add responsive medicine that recognizes people’s lived experiences and supports individual decision making.