Respective prognostic value of genomic grade and histological proliferation markers in early stage (pN0) breast carcinoma.

BACKGROUND: Genomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score. METHODS: A series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up). GG was computed using MapQuant Dx(R). RESULTS: GG was low (GG-1) in 48%, high (GG-3) in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2- tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02). CONCLUSIONS: In a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i) the relatively close prognostic values of GG and Ki67, (ii) the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii) the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma.

Pathologic response to short intensified taxane-free neoadjuvant chemotherapy in patients with highly proliferative operable breast cancer.

OBJECTIVES: Breast cancer treatment relies on 3 major phenotypical subtypes, including the triple-negative (TN), HER2-positive, and hormone receptor-positive (estrogen receptor/progesterone receptor) ones. We retrospectively determined the clinical and pathologic response rates to intensified taxane-free neoadjuvant chemotherapy according to these phenotypical classes in a series of patients with highly proliferative operable breast cancer, and examined the patterns of recurrence. METHODS: Patients with early breast cancer with highly proliferative (S-phase fraction >4%) operable tumors of >3 cm received 4 cycles of intensified neoadjuvant chemotherapy with high-dose cyclophosphamide (doxorubicin 70 mg/m d1, cyclophosphamide 700 mg/m d1/d8, and 5 FU 700 mg/m d1-d5) every 3 weeks. RESULTS: Fifty-five patients were included in the analysis. Patients with TN phenotype experienced a high pathologic complete response (pCR) rate to intensified chemotherapy in comparison with patients with HER2-positive and estrogen receptor/progesterone receptor tumors (47%, 0%, and 12%, respectively). Forty percent of patients with TN breast cancer recurred after a median follow-up of nearly 11 years, but only 22% of those achieving a pCR. CONCLUSIONS: A high pCR rate to short intensified neoadjuvant chemotherapy with high-dose cyclophosphamide was achieved in patients with operable highly proliferative TN breast cancer, and pCR was associated with a low rate of recurrence.

Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options.

The recent literature shows that interest in ocular adnexal lymphomas and their biologic and clinical characteristics--along with their possible association with Chlamydia psittaci infection and therapeutic management with rituximab or anti-Chlamydia psittaci antibiotic therapy--is considerable. These new data have modified the previously reported features of this disease and have made an updated review of the literature necessary. The aims of this review are to present the current knowledge on the biology of these lymphomas, their clinical features and prognostic factors, and the panel of all available treatment options.

[Targeting epidermal growth factor receptor in cancer of the breast]. / Ciblage du récepteur du facteur de croissance épidermique dans les cancers du sein.

The erbB receptor family is part of the receptor tyrosine kinase superfamily and consists of four members erbB. The erbB receptor family has been shown to play an important role in both the development of the normal breast and the pathogenesis and progression of breast cancer. Receptor overexpression has also been shown to be a negative prognostic indicator and to correlate with both tumor invasiveness and a lack of responsiveness to standard treatment, both chemotherapy and hormonotherapy. The targeting of EGFR mainly resides in two approaches: tyrosine kinase inhibition and monoclonal antibodies blocking ligand fixation. Many experimental data support the potential role of targeting EGFR in breast cancer. Particularly tyrosine kinase inhibitors demonstrates activity as single agent or in association with hormonotherapy, chemotherapy and trastuzumab. The association of Iressa with hormonotherapy points out that theses agents may prevent or differ hormonoresistance. Moreover studies in situ carcinoma suggest that tyrosine kinase inhibitors may play a role in chemoprevention. So, targeting EGFR may be indicated in a large spectrum of breast tumors from early to advanced stages, hormone negative or positive breast tumors. However the complexity of erbB network requires the targeting of multiple molecular sites within the network and the characterization of tumor profiles in order to optimally select patients for these therapies.