Lauren Schnaper

Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343

PURPOSE To determine whether there is a benefit to adjuvant radiation therapy after breast-conserving surgery and tamoxifen in women age ≥ 70 years with early-stage breast cancer. PATIENTS AND METHODS Between July 1994 and February 1999, 636 women (age ≥ 70 years) who had clinical stage I (T1N0M0 according to TNM classification) estrogen receptor (ER) -positive breast carcinoma treated by lumpectomy were randomly assigned to receive tamoxifen plus radiation therapy (TamRT; 317 women) or tamoxifen alone (Tam; 319 women). Primary end points were time to local or regional recurrence, frequency of mastectomy, breast cancer-specific survival, time to distant metastasis, and overall survival (OS). RESULTS Median follow-up for treated patients is now 12.6 years. At 10 years, 98% of patients receiving TamRT (95% CI, 96% to 99%) compared with 90% of those receiving Tam (95% CI, 85% to 93%) were free from local and regional recurrences. There were no significant differences in time to mastectomy, time to distant metastasis, breast cancer-specific survival, or OS between the two groups. Ten-year OS was 67% (95% CI, 62% to 72%) and 66% (95% CI, 61% to 71%) in the TamRT and Tam groups, respectively. CONCLUSION With long-term follow-up, the previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains. However, this does not translate into an advantage in OS, distant disease-free survival, or breast preservation. Depending on the value placed on local recurrence, Tam remains a reasonable option for women age ≥ 70 years with ER-positive early-stage breast cancer.

Breast cancer diagnosis and prognosis through quantitative measurements of serum glycan profiles.

BACKGROUND Glycosylated proteins play important roles in cell-to-cell interactions, immunosurveillance, and a variety of receptor-mediated and specific protein functions through a highly complex repertoire of glycan structures. Aberrant glycosylation has been implicated in cancer for many years. METHODS We performed specific MALDI mass spectrometry (MS)-based glycomic profile analyses of permethylated glycans in sera from breast cancer patients (12, stage I; 11, stage II; 9, stage III; and 50, stage IV) along with sera from 27 disease-free women. The serum glycoproteins were enzymatically deglycosylated, and the released glycans were purified and quantitatively permethylated before their MALDI-MS analyses. We applied various statistical analysis tools, including ANOVA and principal component analysis, to evaluate the MS profiles. RESULTS Two statistical procedures implicated several sialylated and fucosylated N-glycan structures as highly probable biomarkers. Quantitative changes according to a cancer stage resulted when we categorized the glycans according to molecular size, number of oligomer branches, and abundance of sugar residues. Increases in sialylation and fucosylation of glycan structures appeared to be indicative of cancer progression. Different statistical evaluations confirmed independently that changes in the relative intensities of 8 N-glycans are characteristic of breast cancer (P < 0.001), whereas other glycan structures might contribute additionally to distinctions in the statistically recognizable patterns (different stages). CONCLUSIONS MS-based N-glycomic profiling of serum-derived constituents appears promising as a highly sensitive and informative approach for staging the progression of cancer.

A cancer-associated PCNA expressed in breast cancer has implications as a potential biomarker

Two isoforms of proliferating cell nuclear antigen (PCNA) have been observed in breast cancer cells. Commercially available antibodies to PCNA recognize both isoforms and, therefore, cannot differentiate between the PCNA isoforms in malignant and nonmalignant breast epithelial cells and tissues. We have developed a unique antibody that specifically detects a PCNA isoform (caPCNA) associated with breast cancer epithelial cells grown in culture and breast-tumor tissues. Immunostaining studies using this antibody suggest that the caPCNA isoform may be useful as a marker of breast cancer and that the caPCNA-specific antibody could potentially serve as a highly effective detector of malignancy. We also report here that the caPCNA isoform functions in breast cancer-cell DNA replication and interacts with DNA polymerase δ. Our studies indicate that the caPCNA isoform may be a previously uncharacterized detector of breast cancer.

Elevated levels of hydroxylated phosphocholine lipids in the blood serum of breast cancer patients.

The difference in serum phospholipid content between stage-IV breast cancer patients and disease-free individuals was studied by employing a combination of chemometric statistical analysis tools and mass spectrometry. Chloroform-extracted serum samples were profiled for their lipid class composition and structure using precursor ion, neutral loss, and product ion tandem mass spectrometric (MS/MS) scanning experiments. Changes in the relative abundance of phospholipids in serum as a consequence of cancer progression, measured through electrospray ionization (ESI) mass spectrometry of flow-injected serum samples collected from 25 disease-free individuals and 50 patients diagnosed with stage-IV breast cancer, were statistically evaluated using principal component analysis (PCA), analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis. Lipids whose abundance changed significantly as a consequence of cancer progression were structurally characterized using product ion spectra, and independently quantified using precursor ion scan experiments against an internal standard of known concentration. Phosphocholine lipids that displayed a statistically significant change as a consequence of cancer progression were found to contain an oxidized fatty acid moiety as determined by MS3 experiments.

A novel reconstructive technique following central lumpectomy.

Breast conservation therapy is a wellestablished treatment method for subareolar breast cancers, provided that the nipple-areola complex is completely removed, adequate surgical margins are obtained following tumor resection, and adjuvant radiation therapy is received. After resection of the central breast and nipple-areola complex, the remaining surgical defect is commonly closed primarily. However, this frequently results in an unattractive deformity, especially with larger subareolar tumors. We describe an immediate reconstructive technique after central lumpectomy and nipple-areola complex resection that demonstrates excellent cosmesis following radiation therapy.

Can older women with early breast cancer avoid radiation

Lancet Oncology, The - In Press.Proof corrected by the author Available online since jeudi 29 janvier 2015

Special Considerations when Treating Breast Cancer in the Elderly

The growing aging population of the U.S. will lead to an absolute and proportional increase in elderly women with breast cancer. While the underlying biologic characteristics of the disease will not likely change, the health status and life expectancy of the patients will improve. Our decisions regarding therapy must take into account not just the disease we are treating, but the characteristics of the host as well.