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Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)



- To estimate the mean change in MRI tumor volume from pretreatment to completion of
preoperative endocrine therapy in estrogen receptor-positive (ER+) ductal carcinoma in
situ (DCIS), as well as to determine whether 3-month change in volume correlates with
6-month change.


- To assess radiographic-pathologic correlation between MRI findings and histopathology,
including the prevalence of occult invasive cancer in patients undergoing neoadjuvant
endocrine therapy for DCIS.

- To compare changes in MRI maximum lesion diameter and mammographic extent at baseline
and following treatment.

- To determine practice patterns of adjuvant hormonal and radiation therapy in patients
who complete neoadjuvant letrozole therapy for DCIS.

- To determine whether Ki67 is reduced with neoadjuvant letrozole treatment for DCIS, and
to compare the reduction in proliferation between radiographic responders and

- To identify baseline IHC and expression biomarkers predictive of response to treatment,
with response determined by extent of Ki67 reduction.

- To examine whether germline polymorphisms are associated with clinical endpoints,
including treatment-related toxicity or efficacy outcomes, or with expression of
biomarkers in serum or tumor.

- To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant
letrozole for ER+ DCIS.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant letrozole orally (PO) once daily (QD) for 3 months. Patients
then undergo MRI with an IV contrast. Patients with progressive disease discontinue
letrozole and undergo surgery. Patients with complete, partial, or stable disease continue
letrozole PO QD for an additional 3 months before undergoing another MRI and surgery.
Patients continue receiving letrozole until the day before surgery.

Surgery (mastectomy or lumpectomy) must be performed within 30 days of the 3- or 6-month

Patients' core biopsy specimen and surgical excision specimen may be collected for
correlative studies.

Patients may complete the Menopause Specific Quality-of-Life Questionnaire (MEMOQOL), the
Brief Pain Inventory (BPI-SF), the Functional Assessment of Cancer Therapy - General
(FACT-G), the Self-Efficacy for Coping with Side Effects, the Medication Taking Behavior
(MMAS), and the Beliefs about Medicines Questionnaires at baseline and periodically during

After completion of study therapy, patients are followed up at 1, 3, and 6 months.

Inclusion Criteria


- Pathologic confirmation of ductal carcinoma in situ (DCIS) without invasive cancer of
the female breast with diagnosis rendered on core biopsy only, completed within 60
days before registration

- Patients diagnosed with DCIS on the basis of surgical biopsy are not eligible
for this study

- Disease stage Tis, N0, M0

- All patients must have had a diagnostic core biopsy with clip placed at time of
biopsy or prior to baseline MRI

- Diagnostic tissue available for correlative studies

- DCIS must express estrogen receptor, as determined by immunohistochemical methods on
the diagnostic pathology sample, according to the local institution's standard

- Greater than or equal to 1% cells will be considered to be positive

- Measurable disease

- Mammographic extent of calcifications must be accurately measurable in at least
one dimension with each lesion ≥ 1 cm and ≤ 5 cm

- DCIS must be visible on MRI without radiographic evidence of invasive cancer

- Patients with palpable DCIS or adenopathy are not eligible to participate


- Patients must be postmenopausal* defined as:

- Age ≥ 55 years and one year or more of amenorrhea

- Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20

- Surgical menopause with bilateral oophorectomy (at least 28 days must elapse
from surgery to time of study registration) NOTE: *The use of GnRH analogs to
achieve postmenopausal status is not allowed.

- ECOG performance status 0 or 1

- ANC ≥ 1,000/μL

- Platelet count ≥ 100,000/μL

- Serum creatinine ≤ 1.7 mg/dL

- Bilirubin ≤ 2.0 mg/dL

- AST/ALT ≤ 2.5 times upper limit of normal

- Serum estradiol level assay < 20 pg/mL

- Required for patients < 55 years of age and one year or more of amenorrhea

- Not pregnant or nursing

- No contraindications to breast MRI

- Women diagnosed with osteoporosis may participate in this trial provided they are
receiving appropriate therapy


- No prior surgical excision in the index breast for ductal carcinoma in situ (DCIS) or
invasive cancer

- Any exogenous hormone therapy must be completed 4 weeks prior to registration

- Any patients with a history of tamoxifen or raloxifene use will be excluded

- No prior neoadjuvant/adjuvant therapy for breast cancer

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

3-month and 6-month radiographic tumor volume

Safety Issue:


Principal Investigator

E. Shelley Hwang, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University



Study ID:




Start Date:

February 2012

Completion Date:

Related Keywords:

  • Breast Cancer
  • ductal breast carcinoma in situ
  • estrogen receptor-positive breast cancer
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma in Situ
  • Carcinoma, Intraductal, Noninfiltrating
  • Carcinoma, Ductal, Breast
  • Carcinoma, Ductal



Mayo Clinic Scottsdale Scottsdale, Arizona  85259
Mayo Clinic Cancer Center Rochester, Minnesota  55905
CCOP - Bay Area Tumor Institute Oakland, California  94609-3305
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
St. Elizabeth Medical Center Edgewood, Kentucky  41017
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Missouri Baptist Cancer Center St. Louis, Missouri  63131
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240
Pardee Memorial Hospital Hendersonville, North Carolina  28791
Bethesda North Hospital Cincinnati, Ohio  45242
Duke Cancer Institute Durham, North Carolina  27710