SAN ANTONIO—Chemoprevention with tamoxifen or anastrozole significantly reduces the risk of invasive breast malignancies in women with atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), and ductal carcinoma in situ (DCIS) , according to a review of clinical trial findings presented at the 2015 San Antonio Breast Cancer Symposium.1
“Large prevention trials support a key role for endocrine therapy in the setting of premalignant lesions and DCIS for the primary prevention of breast cancer and secondary prevention of recurrence in DCIS,” reported E. Shelley Hwang, MD, MPH, of Duke University Medical Center in Durham, NC.
The field will need to more precisely select patients for these treatments, which confer risks of side effects that have resulted in poor uptake of chemoprevention, she said.
The utility of neoadjuvant or primary endocrine therapy for low-risk DCIS is currently under investigation, Dr Hwang reported. “More precise quantification and communication of the risks and benefits of the endocrine therapies will be increasingly needed in order to maximize the benefits of endocrine intervention in this setting.”
The existence of lesions associated with increased risks of invasive breast cancer have long been recognized. “The most frequently encountered are AH, LCIS, and DCIS, although other diagnoses have also been identified,” Dr Hwang noted. She cautioned that these entities are genetically similar and the low concordance of pathologists’ designations of biopsies to these categories illustrates their similarity.
However, these lesions are frequently found incidentally, with uncertain implications for a patient’s risk of breast cancer. Patient management in such cases “has largely consisted of surveillance, sometimes with the addition of endocrine therapy,” said Dr. Hwang. “The selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, have been the mainstay of endocrine therapy in this setting.”
The prospective randomized trial NSABP B-24 randomly assigned 364 women with ER-positive DCIS to receive tamoxifen and 368 to receive placebo, and at a median follow-up of 14.5 years found breast cancer-free survival to be superior among women who received tamoxifen over placebo (hazard ratio [HR] 0.70; 95% CI: 0.5, 0.98; P = .003), she noted.
“Most recently, the role of aromatase inhibitors as chemoprevention in this setting has been studied; the results of IBIS II trial, which randomly assigned 3,864 high risk postmenopausal women to anastrozole or placebo, found a substantial risk reduction in the AI group” (HR 0.47; 95% CI 0.32-0.68, P < .0001), Dr. Hwang noted.
Two prospective clinical trials of adjuvant endocrine therapy (NSABP-B24 and UK/ANZ) found that tamoxifen after lumpectomy for DCIS reduced recurrence of both ipsilateral and contralateral DCIS.
Diagnostic concordance among pathologists in interpreting breast biopsy specimens reveal considerable disagreement when it comes to these lesions. “We’re treating DCIS as a completely different animal from ALH, ADH, LCIS—ignoring the evidence that all of these entities are likely nonobligate precursors for invasion cancer,” Dr Hwang said. “There may be preinvasive lesions with sufficiently low risk for invasion to justify surveillance, especially in patients with competing comorbidities.”
Active surveillance studies (LORIS and LORD/EORTC 1041) for low-risk DCIS are currently open and accruing patients in the United Kingdom and Europe, she concluded.
- Hwang ES. Endocrine management of premalignant lesions and DCIS. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 8, 2015; San Antonio, TX.