A study just published in the prestigious Journal of Clinical Oncology definitively establishes the introduction of low-dose Tamoxifen into clinical practice as post-surgical therapy for the prevention of ductal carcinoma in situ (DCIS), the initial non-invasive form that accounts for around 25% of all breast cancers diagnosed through mammographic screening.
The work, with first author Sara Gandini, epidemiologist and biostatistician, Director of the Unit of Pharmacological and Molecular Epidemiology at the European Institute of Oncology, and last author Andrea De Censi, oncologist and now Director of the Champalimaud Foundation Breast Department, combines individual data from three clinical trials. This is the largest series ever studied to date: 1,545 patients followed for more than nine years, whose data were collected by the Division of Cancer Prevention and Genetics at the IEO, headed by Bernardo Bonanni and Aliana Guerrieri Gonzaga, in collaboration with Ospedali Galliera di Genova and the Champalimaud Foundation.
Because of the importance of the results and immediate impact on clinical practice, the study was selected among the “practice-changing” works and presented in the “Best of ASCO” session at the annual congress of the American Society of Clinical Oncology (ASCO), the most important global event in medical oncology.
Overall, low-dose Tamoxifen significantly reduced breast oncological events, with a particularly marked benefit in postmenopausal women, in whom a 59% reduction in the risk of recurrence or new breast tumour was observed compared with women who did not receive the treatment. In premenopausal women, the greatest benefit was observed in a 55% reduction in tumours arising in the breast opposite to the one already operated on.
“These results definitively show that, in ductal carcinoma in situ and high-risk breast lesions, reducing the dose of hormone therapy with Tamoxifen makes it possible to maintain the preventive efficacy of the standard dose, while substantially reducing side effects. Tamoxifen at 5 mg per day, or at 10 mg every other day, can now be considered a standard of preventive care after surgery,” says Andrea De Censi.
The benefit of high-dose Tamoxifen – 20 mg per day for five years – has been known for decades, but its clinical use has been limited by toxicity, which includes an increased risk of endometrial cancer, venous thromboembolism, hot flushes, gynaecological symptoms and sexual dysfunction.
The study published today finally answers outstanding questions thanks to a combined analysis with the longest follow-up currently available. The results show that the protective effect of low-dose Tamoxifen persists for many years after the end of therapy, without a significant increase in serious adverse events.
“Our study is truly practice changing because it removes the main uncertainties about the use of low-dose Tamoxifen. Today we know more precisely which patients derive the greatest benefit and we can offer a preventive therapy that is more tolerable and sustainable in the long term,” comments Sara Gandini.
According to the researchers, these results also open up new perspectives for primary prevention in healthy women at high risk of developing breast cancer, for example due to family history or the presence of precancerous lesions.
The next step will be to assess increasingly personalised prevention strategies in high-risk women, especially younger patients, who often refuse standard treatment because of side effects. An effective and better tolerated therapy could significantly increase adherence to pharmacological prevention. At the IEO, we are currently extending multicentre studies of low-dose Tamoxifen to healthy women with a familial or germline predisposition to breast cancer.” concludes Bernardo Bonanni.
“This research shows how collaboration between epidemiology, biostatistics, oncology and translational biology can generate concrete results to improve patients’ quality of life and the effectiveness of preventive care,” adds Aliana Guerrieri Gonzaga.
The next step at the Champalimaud Foundation is the implementation of a personalised programme for early diagnosis and risk assessment using artificial intelligence, in order to provide effective and safe preventive therapy for women at increased risk of developing breast cancer.
Original paper here.
Press release developed by Donata Francese, head of External Relations and Press Office of the Istituto Europeo di Oncologia.
