ruxolitinib for premalignant breast disease

Conditions: Ductal Carcinoma In Situ; Atypical Lobular Hyperplasia; Atypical Ductal Hyperplasia; Lobular Carcinoma In Situ

Summary: this study is evaluating how ruxolitinib affects premalignant breast cells. one half of the study participants will receive ruxolitinib for approximately 15 days, and the other half will receive a placebo (sugar pill) for approximately 15 days. once study participants have completed their ruxolitinib or placebo, participants will undergo surgery to remove the premalignant breast tissue.


Eligibility criteria:
inclusion criteria: * have a breast biopsy showing adh (atypical ductal hyperplasia), alh (atypical lobular hyperplasia), lcis (lobular carcinoma in situ), or dcis (ductal carcinoma in situ) requiring surgical excision. microinvasive disease is allowed. * note: tissue from the diagnostic biopsy must be accessible/available for research correlates (i.e., a tissue block or \~10 unstained slides). due to the nature of the study, fewer slides may be accepted with prior permission from the protocol chair if there is insufficient tissue. * women and men age 18 and older. * adequate hematologic and organ function, defined as follows: * absolute neutrophil count ≥ 1500/mm3 * hemoglobin ≥ 9.0 g/dl * platelet levels \>200 x 109/l * total bilirubin ≤ 1.5 x institutional upper limit of normal (uln) * ast/alt ≤ 2.5 x institutional uln * alkaline phosphatase ≤ 5 x institutional uln * creatinine clearance \> 50 ml/min as calculated by the cockcroft-gault method * willing to not use concomitant strong cyp3a4 inhibitors as this could interfere with the metabolism of ruxolitinib (i.e azole antifungals, clarithromycin, conivaptan, grapefruit juice, mibefradil, nefazodone, protease inhibitors, telithromycin). * women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. * if the patient undergoes germline genetic testing, the results must be received prior to randomization, as the results may affect the surgical approach and, in turn, the date of surgical excision. * patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign a written informed consent document. exclusion criteria: * treatment with selective estrogen receptor modulators (serms) or aromatase inhibitors for breast cancer prevention within 1 year prior to starting study treatment. * treatment with any other investigational agents within 30 days of starting study treatment. * current diagnosis of invasive breast cancer (current microinvasive disease is allowed), or previous history of invasive breast cancer diagnosed within the last 5 years. note: if previous history of er+ invasive breast cancer diagnosed \> 5 years ago, patient must be off endocrine therapy for at least 1 year prior to starting study treatment. * uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, end stage renal disease (esrd), or psychiatric illness/social situations that would limit compliance with study requirements. * women who are pregnant or nursing. * hiv-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ruxolitinib. * prior or current treatment with a jak inhibitor, for any indication. * known active hepatitis b or c.

Keywords: premalignant breast disease alh adh dcis lcis breast cancer prevention ruxolitinib