S1007: A Phase III Randomized Clinical Trail of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients with 1-3 Positive Nodes, Hormone Receptor-Positive and HER2 Negative Breast Cancer with recurrence Score (RS) of 25 or less

Summary

this trial will use the regimens that have proven to be of greater benefit than earlier chemotherapy regimens in modern randomized trials. The study will use a simple parallel two-group randomization to chemotherapy followed by endocrine therapy or endocrine therapy alone in a lower risk, 1-3 node-positive population (identified by intermediate or low Recurrence Score) to determine if modern chemotherapy is efficacious and to identify those patients who will
benefit from the addition of chemotherapy.

Participant Eligibility

-->Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, as determined by IHC or non-amplified FISH or CISH for screening. Estrogen and progesterone positivity must be assessed according to ASCO/CAP guidelines (assays are considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal [normal epithelial elements] and external controls). If HER2 IHC is 2+, FISH / CISH must be performed and must not be positive (must be a ratio of ≤ 2.2), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.

-->Patients with FISH/CISH in the indeterminate range (a ratio of 1.8 to 2.2) are eligible for the study only if they are not planning to receive treatment with trastuzumab.

---Patients with multifocal, multicentric and synchronous bilateral breast cancers are allowed.
• Multifocal disease is defined as more than one invasive cancer < 2 cm from the largest lesion within the same breast quadrant. (NOTE: The Oncotype DX® testing must be completed on the largest lesion.)

• Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants. (NOTE: Oncotype DX® testing should be completed on all tumors and the determination for eligibility should be made on the highest recurrence score.)

• Synchronous bilateral disease is defined as invasive breast cancer with bilateral positive lymph nodes, diagnosed within 30 days of each other. (NOTE: The Oncotype DX® testing should be completed on both tumors and the tumor with the
highest recurrence score should be used.)


-->Patients with positive sentienel node are not required to undergo full axillary lymph node dissection,

--> Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph
node dissection (ALND).

--> Patients must have at least one, but no more than three known positive lymph nodes (pN1mi, pN1a, pN1b or pN1c),

--.>Axillary node evaluation is to be performed per the standard of care at each insititution
.
--> Patients must not have inflammatory breast cancer and must not have metastatic
disease.

--> Patients with a prior diagnosis of DCIS are eligible if they received mastectomy
alone (no therapeutic radiation or endocrine therapy). Radiation in the opposite breast is
acceptable

-->Patients must have had either breast-conserving surgery with planned radiation therapy
or total mastectomy (with or without planned postmastectomy radiation).

-->Patients must have clear margins.(as per local institutional guidelines).

--> Registration of patients who have not yet undergone Oncotype DX® screening must occur no later than 56 days after definitive surgery.
(For all patients, Step 2 Registration must occur within 84 days after definitive surgery.)
If the Oncotype DX® Breast Cancer Assay has not been performed, patients must be willing to
submit tissue samples for testing to determine the Recurrence Score value.
-->ALLPatients must be females ≥ 18 years of age.
--->Patients who are able to complete a questionnaire in English must be offered the opportunity to participate in the Quality of Life and Economic Substudy

The Quality of Life and Economic Substudy is available to U.S. institutions only. This information was added to this section replacing the following sentence: "(EXCEPTION: Patients enrolling through NCIC-CTG will not participate in the Quality of Life and Economic Substudy.)".


---->Patients with multifocal, multicentric, and synchronous bilateral breast cancers are allowed