The prognostic significance of determining DNA content in breast cancer by DNA image cytometry: the role of high grade aneuploidy in node negative breast cancer

10551 Background: Prediction of late metastasis is of clinical relevance in breast cancer. However, systematic genome-wide studies to identify genes associated with increased risk of metastasis 5 or more years after surgery are scarce. Methods: We examined the natural course of disease in three previously published cohorts (Mainz, Rotterdam, Transbig) including 766 node-negative breast cancer patients with gene array data who did not receive systemic chemotherapy in the adjuvant setting. We established a Cox regression based method adjusted for multiple testing that identified genes predicting late metastasis (5 or more years after surgery). Only those genes were accepted that showed similar results in all three cohorts. Metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Results: We identified 9 genes [ABCC5 (Hazard Ratio (HR) 2.19, p=0.003), EDDM3B (HR 3.58, p=0.044), RAD23B (HR 0.37, p<0.001), XYLT2 (HR 2.19, p=0.027), DDX18 (HR 0.35, p=0.006), GPBP1L1 (HR 0.20, p=0.018), UBB (HR 9.73, p=0.025), RPS24 (HR 0.20, p=0.050), GPC1 (HR 2.36, p=0.013)] predicting late metastasis. These genes retained their independent prognostic significance after adjustment for established clinical factors (age, tumor size, grade, hormone receptor status, HER2) and biological motives like estrogen receptor, proliferation, B or T cells. These late-type genes are largely associated with resistance to hypoxia, apoptosis and DNA damage, suggesting that they might contribute to persistence of disseminated tumor cells. Conclusions: Genes associated with late metastasis offer a perspective to identify breast cancer patients suitable for additional and prolonged therapies.

Download Full-text

Predictors of post-mastectomy radiation (PMRT) in node-negative breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12608 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12608-e12608

Author(s):

Laura Sheriff ◽

Erin Cordeiro ◽

Jacob Hardy ◽

Amanda Roberts

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Sentinel Lymph Node Biopsy ◽

Lymph Node Biopsy ◽

High Grade ◽

Breast Cancer Patients ◽

Node Negative ◽

Node Biopsy ◽

Node Negative Breast Cancer

e12608 Background: Post-mastectomy radiation (PMRT) reduces the risk of locoregional failure for women with an elevated risk of recurrence from breast cancer. Therefore, PMRT is often indicated for women with node positive breast cancer including those with only 1-3 nodes involved. The need for PMRT in node negative breast cancer patients is less established. The objective of our study was to review the predictors of PMRT in women with node-negative breast cancer and evaluate the overall recurrence rates. Methods: A retrospective chart review was completed. Women with node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy at a regional breast cancer center between January 1st,2011 and December 31st, 2017 were included. Patient and tumor characteristics, treatment details and recurrence data were recorded. The primary outcome was recommendation of PMRT. Univariate analysis was completed and then a multivariable logistic regression was completed to determine independent predictors for PMRT. Results: Overall, 235 women with node-negative breast cancer underwent mastectomy and sentinel lymph node biopsy during the study period. Forty-three (18.3%) patients were recommended to undergo PMRT, with 39 of the 43 patients completing the recommended treatment. PMRT was offered more often to younger women (p<0.001), women with multifocal/centric disease (p=0.002), large tumors (p<0.001), high grade tumors (p < 0.001), lymphovascular positive tumors (p=0.04) and estrogen-negative disease (p =0.017). On multivariable analysis, the odds of radiation recommendation were highest for patients with high grade disease (OR 5.81, 95%CI: 2.08 – 16.20) followed by multifocal/centric disease (OR 3.12, 95%CI: 1.26 – 7.70). There were no differences in overall recurrence between patients who underwent PMRT versus those who did not have PMRT (p = 0.31). Conclusions: A moderate percentage of node negative patients are offered PMRT. Independent predictors for recommendation of PMRT in node negative patients are: decreasing age, increasing tumor size, multifocal/centric disease and higher grade disease. Surgeons can use this information to counsel patients regarding the possible need for PMRT, especially in the setting of planned immediate reconstruction.

Download Full-text

Influence of Endocrine-Related Factors on Response to Perioperative Chemotherapy for Patients With Node-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.21.4141 ◽

2001 ◽

Vol 19 (21) ◽

pp. 4141-4149 ◽

Cited By ~ 59

Author(s):

Marco Colleoni ◽

Shari Gelber ◽

Alan S. Coates ◽

Monica Castiglione-Gertsch ◽

Richard D. Gelber ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Treatment ◽

Steroid Hormone ◽

Menopausal Status ◽

Prognostic Significance ◽

Steroid Hormone Receptors ◽

Perioperative Chemotherapy ◽

Primary Tumors ◽

Node Negative ◽

Node Negative Breast Cancer

PURPOSE: We investigated tumor- and patient-related features that might influence the response to perioperative chemotherapy (PeCT) compared with no adjuvant therapy for patients with node-negative breast cancer. PATIENTS AND METHODS: A total of 1,275 patients were randomized to either no adjuvant treatment (427 patients) or PeCT (848 patients). The following variables thought to have prognostic significance were evaluated: grade, tumor size, estrogen (ER) and progesterone receptor (PgR) content (absent; low, 1 to 9 fmol/mg cytosol protein; or positive, ≥ 10 fmol/mg cytosol protein), c-erbB-2 overexpression, menopausal status, and age. Cox proportional hazards regression models were used to assess the relative influence of these factors to predict the effect of PeCT on disease-free survival (DFS). Median follow-up was 13.5 years. RESULTS: The 10-year DFS percentage for 692 premenopausal patients did not significantly differ between the PeCT and no-adjuvant-treatment groups: 61% and 59%, respectively (relative risk [RR], 0.95; 95% confidence interval [CI], 0.75 to 1.20; P = .70). No predictive factors were identified. For 583 postmenopausal patients, 10-year DFS percentages for the groups were 63% and 58%, respectively (RR, 0.75; 95% CI, 0.58 to 0.93; P = .03). The absence of expression of ER, PgR, or both ER and PgR was the most important factor predicting improved outcome with PeCT among postmenopausal patients. The 10-year DFS percentages were 85% and 53% for the steroid hormone receptor–absent cohort of treated and untreated patients, respectively (RR, 0.18; 95% CI, 0.06 to 0.49; P = .0009). CONCLUSION: The role of PeCT should be explored for patients whose primary tumors do not express steroid hormone receptors, because it is likely that early initiation of treatment is exclusively relevant for such patients.

Download Full-text