Ruxolitinib for Premalignant Breast Disease

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.