In the words of my mentor, “the best cancer is no cancer.” So, in that vein, many of us were delighted to see practice-changing breast cancer prevention work presented at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
Presented this year by Dr. Andrea DeCensi and colleagues was a randomized trial of low dose tamoxifen, so called “babyTam” in the spirit of baby aspirin. We have known for many years about the preventive effects of full dose tamoxifen (20-milligrams daily) to prevent breast cancer recurrence and new primaries, but uptake remains disappointingly low. For example, the substantial and prolonged benefit of endocrine therapy for breast cancer prevention has been defined in multiple randomized studies, including NSABP P-1, IBIS-I and IBIS-II, STAR and MAP3, but uptake hovers at only around 4% of eligible women.
This low uptake is also notable because endocrine prophylaxis is also in multiple guidelines, including American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), and the United States Preventive Services Taskforce (USPSTF), among others. This current study sought to determine if a lower dose of tamoxifen may cause fewer side effects, but enhance adherence while not compromising on the preventive effects of tamoxifen. This Italian study randomized 500 women aged 75 or lower with atypical ductal hyperplasia, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS), all of which are predictors of a higher-than-average risk of invasive breast cancer. Patients were randomized to 5-milligrams of tamoxifen daily or placebo for three years. All subjects had at least two years of follow up.
The primary endpoint was incidence of invasive breast cancer or DCIS. Median follow up was good at 5.1 years. There were 42 events which occurred in the study follow up time. And the treatment with babyTam was effective – with reduction by 52% in all breast events and reduction by 76% in contralateral breast cancer. And the treatment was very well tolerated with the only significant increased side effect of one additional hot flash per day in the participants who took the babyTam. Notably, risk of endometrial cancer and deep venous thrombosis or pulmonary embolism were not increased and actually occurred less frequently than would be expected with full dose tamoxifen.
The investigators then did subgroup analyses to understand who is more likely to benefit from babyTam. The benefit was strongly in women over 50 years, never smokers, those with higher baseline Ki-67 percentage in their precursor breast lesion (more than 10%) and those women with baseline hot flashes. The investigators hypothesized that tobacco may raise body estrogen levels, thereby negating the effects of tamoxifen, which is an estrogen receptor modulator. The discussant, Dr. Erin Hofstater from Yale University, concluded that babyTam is well tolerated and has low toxicity and ready for prime time use in women who cannot tolerate full dose tamoxifen or where other agents are not available (for example, due to insurance coverage). She further stated that updates are forthcoming to the ASCO and NCCN guidelines to reflect babyTam as a treatment options. She encouraged direct comparison of babyTam to full dose tamoxifen with future studies. Notably, tamoxifen does not come in a 5-milligram tablet size, so a patient can either take 10-milligrams every other day or split a 10-milligram tablet in half daily. In addition to oncologists and breast surgeons, Primary Care physicians should feel empowered to recommend and discuss endocrine prophylaxis for their patients who have LCIS, DCIS or breast atypia, including the new option of babyTam, with tamoxifen at 5-milligrams daily for three years.
Illustration by Jennifer Bogartz