This new information makes me crazy!

I know I shouldn't look back. It is too late to change my mind about chemo but this new paper makes me question the logic behind the decision making of both my MO and my second opinion MO. Both based their recommendation on RX Ponder and my Oncotype DX results. I had two positive nodes, one was a 1.7 cm tumor. The second was micromets. I had extensive LVI which is why I ended up with a UMX after my LX. Here is what makes me crazy. Full article Use of Biomarkers to Guide Decisions on Adjuvant Therapy for women with early stage breast cancer

CLINICAL QUESTION 1

For women with early-stage invasive breast cancer and with known ER/PgR and HER2 status, which other biomarkers have demonstrated clinical utility to guide decisions on the need for adjuvant systemic therapy?

Recommendation 1.1

If a patient has ER/PgR-positive, HER2-negative (node-negative) breast cancer, the clinician may use the 21-gene recurrence score (RS; Oncotype DX; Genomic Health, Redwood City, CA) to guide decisions on adjuvant systemic chemotherapy. Type: evidence based. Evidence quality: high. Strength of recommendation: strong.

Clinical interpretation of literature review.

The 21-gene RS assists with the decision of adjuvant chemotherapy in patients with ER/PgR-positive, HER2-negative (node-negative) breast cancer.^20-22 Chemotherapy is indicated in patients with a high RS and is not indicated in patients with a low RS. Recommendations for adjuvant chemotherapy in patients with an intermediate RS may be determined by TAILORx (Trial Assigning Individualized Options for Treatment; ClinicalTrials.gov identifier: NCT00310180).

Recommendation 1.2

If a patient has ER/PgR-positive, HER2-negative (node-positive) breast cancer, the clinician should not use the 21-gene RS to guide decisions on adjuvant systemic chemotherapy. Type: evidence based. Evidence quality: intermediate. Strength of recommendation: moderate.

Clinical interpretation of literature review.

The 21-gene RS might identify patients with ER/PgR-positive, HER2-negative (node-positive) breast cancer for whom chemotherapy might not be recommended on the basis of either prognosis (that the patient does not need chemotherapy) or prediction (that chemotherapy might have little or no benefit).²³ Although the 21-gene RS is prognostic in patients with node-positive disease (patients with low RS have a better prognosis than patients with high RS), patients with node-positive disease but low RS have a worse prognosis than patients with node-negative, low RS disease. This different baseline prognosis for node-positive compared with node-negative disease may alter the balance of prognostic and predictive factors that lead to an overall recommendation to withhold or administer chemotherapy. For node-positive breast cancer, one must simultaneously consider the prognostic effects of the number of positive nodes and the 21-gene RS as well as any predictive value of the 21-gene RS.

The panel identified two main contexts in which a recommendation to withhold chemotherapy for patients with node-positive breast cancer might be considered. One context is that of a subgroup of patients with limited node-positive disease (one positive lymph node with a small deposit of cancer) for whom the prognostic role of the 21-gene RS might be similar to that for patients with node-negative disease. The panel also considered whether there might be a group of patients with more extensive nodal involvement, but for whom the predictive role of the 21-gene RS could identify whether chemotherapy would be ineffective, even though the patients' prognosis is unsatisfactory. However, the panel believed that more data are needed to determine the specific combinations of axillary nodal disease extent and RS that would define these patient subgroups.

The panel recognized that data from the Southwest Oncology Group (SWOG) S8814 and Arimidex, Tamoxifen, Alone or in Combination (ATAC) trials suggest that patients with only one to three positive nodes may have similar prognoses to those with negative nodes.^22,23 However, the panel could not rule out the possibility of additional variation in prognosis due to number of positive nodes and did not reach consensus on withholding chemotherapy for patients with one or two positive axillary micrometastases and low RS on the basis of prognosis rather than prediction. The majority of panel members believed that additional high levels of evidence are necessary to recommend the application of this assay for that use context.

With regard to the predictive role of the 21-gene RS for chemotherapy, several studies suggested that cancers with high ER/PgR and low HER2 and protein encoded by the MKI67 gene (Ki-67) might be less chemosensitive than those with low ER/PgR and high HER2 and Ki-67.⁷⁰ Indeed, data generated from the National Surgical Adjuvant Breast and Bowel Project trial B20 suggested that adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy is ineffective in patients with node-negative disease and low RS, whereas it is effective in those with high RS. Likewise, the data from SWOG S8814 in patients with node-positive disease were similar. However, the B20 data are confounded by the data set originally used to generate the 21-gene RS algorithm. The results from SWOG S8814 must be considered hypothesis generating because the number of samples analyzed in each RS subgroup was small, there was no additional prediction beyond 5 years, and the risks of systemic recurrence continues to be high for patients with node-positive disease.

Because widespread use of adjuvant chemotherapy has had such a profound effect on reducing breast cancer mortality,^21,23 the panel believed that clinicians must take a cautious approach to withholding it from patients with node-positive disease. However, there may be some patients for whom the relative benefit of chemotherapy does not justify the risk of toxicity. The RxPONDER trial (Rx for Positive Node, Endocrine Responsive Breast Cancer; ClinicalTrials.gov identifier: NCT01272037) currently is accruing patients to answer this question and to identify the cutoff of the RS for which chemotherapy is beneficial for patients with one to three positive nodes. The Data Supplements provide more detailed discussion on this issue.