Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors

• Published in: Journal of clinical oncology Vol. 29; no. 33; pp. 4365 - 4372
• Main Authors: GONG TANG, CUZICK, Jack, COSTANTINO, Joseph P, DOWSETT, Mitch, FORBES, John F, CRAGER, Michael, MAMOUNAS, Eleftherios P, SHAK, Steven, WOLMARK, Norman
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20-11-2011
• Subjects: Aged; Biological and medical sciences; Breast Neoplasms - chemistry; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Female; Gynecology. Andrology. Obstetrics; Humans; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - etiology; Original Reports; Predictive Value of Tests; Proportional Hazards Models; Receptors, Estrogen - analysis; Risk Assessment; Tumors; Human; Estrogen receptor; Relapse; Breast disease; Early stage; Breast cancer; Malignant tumor; Mammary gland diseases; Chemotherapy; Score; Treatment; Cancerology; Risk factor; Cancer; Hormonal receptor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.35.3714

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value.
From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20.
RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037).
RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.