Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0-17), intermediat

p53 Expression in Node-Positive Breast Cancer Patients: Results from the Cancer and Leukemia Group B 9344 Trial (159905)

p53 as a prognostic and predictive factor in early stage breast cancer, has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel (CALGB 9344, INT0148)

Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342

INTRODUCTION: The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. METHODS: Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m(2), adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. RESULTS: Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). CONCLUSION: None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival

Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0–17), intermediate (18–30), and high (31) to predict chemotherapy benefit. Our goal was to determine the association between histomorphology, immunohistochemistry, and RR. We retrospectively identified 536 patients with ER+ and LN− breast cancers that underwent Oncotype testing from 2006 to 2013. Tumor size ranged from 0.2 cm to 6.5 cm (mean = 1.3 cm) and was uniform in all 3 categories. The carcinomas were as follows: ductal = 63.2%, lobular = 11.1%, and mixed = 35.7%. The RR correlated with the Nottingham grade. Increasing RR was inversely related to PR positivity but directly to Her2 positivity. Of the morphologic parameters, a tubular(lobular) morphology correlated only with low-intermediate scores and anaplastic type with intermediate-high scores. Other morphologies like micropapillary and mucinous were uniformly distributed in each category. Carcinomas with comedo intraductal carcinoma were more likely associated with high RR. Forty-four patients with either isolated tumor cells or micrometastases were evenly distributed amongst the 3 RR. While there was only 1 ER discrepancy between our immunohistochemistry (3+ 80%) and Oncotype, up to 8% of PR+ cases (mean = 15%, median = 5%) and 2% of HER2+ cases were undervalued by Oncotype

A Unique Presentation of Occult Primary Breast Cancer with a Review of the Literature

We are reporting a case of a 34-year-old woman with occult primary breast cancer discovered after initially presenting with neurological symptoms. She was successfully treated with neoadjuvant chemotherapy followed by definitive axillary lymph node dissection and ipsilateral whole breast radiotherapy. The case presented is unique due to the rarity of occult primary breast cancer, especially in light of her initial confounding neurological signs and symptoms, which highlights the importance of careful staging

Defective expression of cellular retinol binding protein type 1 and retinoic acid receptors α2, β2, and ǵ2 in human breast cancer cells

Because the retinoic acid (RA) signaling pathway regulates cell proliferation and differentiation, inactivation of genes integral to the pathway represents a potential mechanism of carcinogenesis. We have studied in human breast cancer cells (T47D, MCF‐7, ZR75‐1, MDA‐MB‐231, and BT20) the expression of a subset of retinoid signaling genes that are themselves transcriptionally up‐regulated by RA, the cellular retinol binding protein type I (CRBPI) and the RA receptors (RARs) (α2, β2, and ǵ2. We find that constitutive expression of these genes is low or undetectable, and that expression levels are seldom responsive to 24 h treatment with 1 μM all‐trans or 9‐cis RA (Northern blot analysis). This is in contrast to breast fibroblasts, which show RA‐de‐ pendent expression of all four genes under the same conditions. Moreover, normal human breast epi‐thelial cells express CRBPI and RARβ2 at the mRNA level, suggesting that loss of expression of these genes is tied to malignant transformation. RARβ2, but not CRBPI, was also expressed in RA‐treated MTSV1‐7 cells, an immortalized but nontumorigenic luminal epithelial cell line. Lack of CRBPI and RARβ2 expression in cancer cells was not due to general impairment of RA signaling, as shown by RA activation of a RARE3‐tk‐CAT reporter in a subclone of MDA‐MB‐231 cells that did not express either CRBPI or RARβ2. These results suggest that at least two independent defects in the expression of proteins that function in retinoid signaling may be involved in breast carcinogenesis.—Jing, Y., Zhang, J., Blei‐ weiss, I. J., Waxman, S., Zelent, A., and Mira‐y‐ Lopez, R. Defective expression of cellular retinol binding protein type I and retinoic acid receptors a2, β2, and ǵ2 in human breast cancer cells. FASEB J. 10,1064‐1070 (1996