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Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)

18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)



- To determine whether letrozole-induced reduction of Ki67 in postmenopausal women with
estrogen receptor (ER)-positive and HER2-negative, resectable, stage I, II, or III
breast cancer correlates with the OncotypeDX assay recurrence score.

- To identify a recurrence risk biomarker profile using RNA microarray.


- To determine the in situ apoptotic effect of letrozole in these patients.

- To correlate the in situ apoptotic effect of letrozole with OncotypeDX assay recurrence
score and RNA profiles.

OUTLINE: Patients receive oral letrozole once daily for 7-21 days in the absence of disease
progression or unacceptable toxicity. Within 24 hours after the last dose of letrozole,
patients undergo total mastectomy or segmental resection with lymph node evaluation.

Pre-treatment diagnostic breast tissue is obtained. Patients undergo treatment and then
undergo standard of care mastectomy or lumpectomy. Pre and post treatment tumor tissue
samples are analyzed for Ki67 and caspase 3 by immunohistochemistry; RNA microarray; and
OncotypeDX assay (a reverse transcriptase-polymerase chain reaction [RT-PCR] assay of 21
prospectively selected genes).

Inclusion Criteria


- Diagnosis of invasive breast cancer

- Clinical stage I, II, or III disease

- Resectable disease

- Measurable disease, defined as a mass that can be reproducibly measured by physical
examination and/or ultrasound and is at least 1 cm in size by ultrasound

- Patients with measurable residual tumor at the primary site allowed

- Estrogen receptor-positive tumor by immunohistochemistry (IHC)

- HER2-negative tumor by Herceptest (0 or +1) OR HER2 not overexpressed by fluorescence
in situ hybridization (FISH)

- Planning to undergo surgical treatment with either segmental resection or total
mastectomy with or withoutlymph node evaluation

- Must have core biopsies from the time of diagnosis available (may include sections of
paraffin-embedded material)

- Prior contralateral breast cancer allowed provided there is no evidence of recurrence
of the initial primary breast cancer

- Patients with locally advanced disease who are candidates for preoperative
chemotherapy at the time of initial evaluation are not eligible

- Locally advanced disease is defined by any of the following:

- Primary tumor ≥ 5 cm (T3)

- Tumor of any size with direct extension to the chest wall or skin (T4a-c)

- Inflammatory breast cancer (T4d)

- Fixed axillary lymph node metastases (N2)

- Metastasis to ipsilateral internal mammary node (N3)

- No locally recurrent disease

- No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain


- ECOG performance status 0-1

- Postmenopausal, as defined by any of the following:

- 55 years of age and over

- Under 55 years of age and meets 1 of the following criteria:

- Amenorrheic for at least 12 months

- Follicle-stimulating hormone (FSH) ≥ 40 IU/L and estradiol levels ≤ 20 IU/L

- Has undergone prior bilateral oophorectomy or radiation castration AND has been
amenorrheic for at least 6 months

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- SGOT and SGPT ≤ 1.5 times ULN

- Creatinine ≤ 1.5 t times ULN

- Able to swallow and retain oral medication

- No serious medical illness that, in the judgment of the treating physician, places
the patient at high risk for operative mortality

- No malabsorption syndrome, ulcerative colitis, or other disease significantly
affecting gastrointestinal function

- No other malignancy within the past 5 years except for completely resected
nonmelanoma skin cancer or successfully treated in situ carcinoma

- No dementia, altered mental status, or any psychiatric condition that would preclude
the understanding or rendering of informed consent

- No severe uncontrolled malabsorption condition or disease (i.e., grade II/III
diarrhea, severe malnutrition, or short gut syndrome)


- See Disease Characteristics

- At least 21 days since prior tamoxifen or raloxifene as a preventive agent

- At least 7 days since prior hormone replacement therapy (e.g., conjugated estrogens

- No prior resection of the stomach or small bowel

- More than 30 days or 5 half-lives, whichever is longer, since prior investigational

- No prior chemotherapy for this primary breast cancer

- No other concurrent investigational agents

- No other concurrent anticancer therapy (e.g., chemotherapy, radiotherapy,
immunotherapy, hormonal therapy, or any other biologic therapy)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative

Outcome Description:

Ki67 index is measured by counting the percentage of cells staining for Ki67 in a section of breast tisse. The number of stained cells will be compared in tissue that is hormone receptor-postive tissue to tissue that is hormone receptor negative.

Outcome Time Frame:

day 7 to day 21

Safety Issue:


Principal Investigator

Ingrid Meszoely, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2008

Completion Date:

December 2014

Related Keywords:

  • Breast Cancer
  • stage IA breast cancer
  • stage IB breast cancer
  • stage II breast cancer
  • stage III breast cancer
  • HER2-negative breast cancer
  • estrogen receptor-positive breast cancer
  • Breast Neoplasms



Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Emory University Atlanta, Georgia  30322
Lankenau Hospital Wynnewood, Pennsylvania  19096
Allegheny Cancer Center Pittsburgh, Pennsylvania  15212-4772
Vanderbilt-Ingram Cancer Center at Franklin Nashville, Tennessee  37064
Surgical Associates, Inc. (Tulsa) Tulsa, Oklahoma  74136
Bryn Mawr Wynnewood, Pennsylvania  19010
Vanderbilt-Ingram Cancer Center, One Hundred Oaks Nashville, Tennessee  37204