Georges Vlastos

Undertreatment Strongly Decreases Prognosis of Breast Cancer in Elderly Women

PURPOSE No consensus exists on therapy of elderly cancer patients. Treatments are influenced by unclear standards and are usually less aggressive. This study aims to evaluate determinants and effect of treatment choice on breast cancer prognosis among elderly patients. PATIENTS AND METHODS We reviewed clinical files of 407 breast cancer patients aged >/= 80 years recorded at the Geneva Cancer Registry between 1989 and 1999. Patient and tumor characteristics, general health status, comorbidity, treatment, and cause of death were considered. We evaluated determinants of treatment by logistic regression and effect of treatment on mortality by Cox model, accounting for prognostic factors. RESULTS Age was independently linked to the type of treatment. Overall, 12% of women (n = 48) had no treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery only, 33% (n = 133) had mastectomy, 14% (n = 57) had breast-conserving surgery plus adjuvant therapy, and 2% (n = 9) received miscellaneous treatments. Five-year specific breast cancer survival was 46%, 51%, 82%, and 90% for women with no treatment, tamoxifen alone, mastectomy, and breast-conserving surgery plus adjuvant treatment, respectively. Compared with the nontreated group, the adjusted hazard ratio of breast cancer mortality was 0.4 (95% CI, 0.2 to 0.7) for tamoxifen alone, 0.4 (95% CI, 0.1 to 1.4) for breast-conserving surgery alone, 0.2 (95% CI, 0.1 to 0.7) for mastectomy, and 0.1 (95% CI, 0.03 to 0.4) for breast-conserving surgery plus adjuvant treatment. CONCLUSION Half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence. Treatments need to be adapted to the patients health status, but also should offer the best chance of cure.

Complete Excision of Primary Breast Tumor Improves Survival of Patients With Metastatic Breast Cancer at Diagnosis

PURPOSE Surgery of the primary tumor usually is not advised for patients with metastatic breast cancer at diagnosis because the disease is considered incurable. In this population-based study, we evaluate the impact of local surgery on survival of patients with metastatic breast cancer at diagnosis. METHODS We included all 300 metastatic breast cancer patients recorded at the Geneva Cancer Registry between 1977 and 1996. We compared mortality risks from breast cancer between patients who had surgery of the primary breast tumor to those who had not and adjusted these risks for other prognostic factors. RESULTS Women who had complete excision of the primary breast tumor with negative surgical margins had a 40% reduced risk of death as a result of breast cancer (multiadjusted hazard ratio [HR], 0.6; 95% CI, 0.4 to 1.0) compared with women who did not have surgery (P = .049). This mortality reduction was not significantly different among patients with different sites of metastasis, but in the stratified analysis the effect was particularly evident for women with bone metastasis only (HR, 0.2; 95% CI, 0.1 to 0.4; P = .001). Survival of women who had surgery with positive surgical margins was not different from that of women who did not have surgery. CONCLUSION Complete surgical excision of the primary tumor improves survival of patients with metastatic breast cancer at diagnosis, particularly among women with only bone metastases.

Older Female Cancer Patients: Importance, Causes, and Consequences of Undertreatment

Despite increased interest in treatment of senior cancer patients, older patients are much too often undertreated. This review aims to present data on treatment practices of older women with breast and gynecologic cancers and on the consequences of undertreatment on patient outcome. We also discuss the reasons and validity of suboptimal care in older patients. Numerous studies have reported suboptimal treatment in older breast and gynecologic cancer patients. Undertreatment displays multiple aspects: from lowered doses of adjuvant chemotherapy to total therapeutic abstention. Undertreatment also concerns palliative care, treatment of pain, and reconstruction. Only few studies have evaluated the consequences of nonstandard approaches on cancer-specific mortality, taking into account other prognostic factors and comorbidities. These studies clearly showed that undertreatment increased disease-specific mortality for breast and ovarian cancers. For other gynecological cancers, data were insufficient to draw conclusions. Objective reasons at the origin of undertreatment were, notably, higher prevalence of comorbidity, lowered life expectancy, absence of data on treatment efficacy in clinical trials, and increased adverse effects of treatment. More subjective reasons were putative lowered benefits of treatment, less aggressive cancers, social marginalization, and physicians beliefs. Undertreatment in older cancer patients is a well-documented phenomenon responsible for preventable cancer deaths. Treatments are still influenced by unclear standards and have to be adapted to the older patients general health status, but should also offer the best chance of cure.

Prognostic Factors in Node-Negative Breast Cancer: A Review of Studies With Sample Size More Than 200 and Follow-Up More Than 5 Years

ObjectiveTo review the published literature on prognostic factors in patients with node-negative breast cancer, focusing principally on recent studies with large sample sizes and extended follow-up periods. Summary Background DataAlthough numerous studies have examined prognostic factors in patients with breast cancer, relatively few have dealt specifically with node-negative disease, and interpretation has been limited by small sample size and limited follow-up times. MethodsA review of the Medline database from 1996 to 2000 was undertaken, with additional papers published before 1996 identified through review articles. For inclusion in the analysis, papers needed to meet the following core criteria: 200 or more node-negative patients with invasive breast carcinoma; median follow-up time at least 5 years; method of testing and cut-off points specified; overall survival and/or disease-free survival specified; and relative risk or statistical probability values given for comparisons. ResultsThree or more papers that met the core criteria were retrieved for each of 11 potential prognostic factors. Of these, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcomes; HER2/ neu and DNA ploidy showed no significant association; and estrogen receptor status and p53 showed mixed results. Lack of standardization in measurement techniques for many of the markers, including cathepsin-D, Ki-67, HER2/ neu, and p53, limited their current clinical usefulness. ConclusionsIn large studies with extended follow-up periods, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcome measures in patients with early-stage node-negative breast cancer. Because of technical difficulties and variations in the measurement of many of these factors, tumor size and tumor grade remain the only markers that currently have broad clinical usefulness for this patient group.

Long-term complications associated with breast-conservation surgery and radiotherapy.

Background Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications.

Lymph Node Ratio as an Alternative to pN Staging in Node-Positive Breast Cancer

PURPOSE In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points. PATIENTS AND METHODS From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups. RESULTS Optimal cutoff points classified patients into low- (< or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively. CONCLUSION LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging.

Long-term survival after an aggressive surgical approach in patients with breast cancer hepatic metastases.

AbstractBackground: Metastatic breast cancer is generally believed to be associated with a poor prognosis. Therapeutic advances over the past two decades, however, have resulted in improved outcomes for selected patients with limited metastatic disease. Methods: Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases. Results: Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates. Conclusions: In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.

Prognostic Value of Nodal Ratios in Node-Positive Breast Cancer

PURPOSE The American Joint Committee on Cancer staging system for breast cancer was recently updated to reflect the impact of increasing the absolute number of positive lymph nodes on prognosis. However, numerous studies suggest that nodal ratios (absolute number of involved nodes-number of nodes resected) may have greater prognostic value than absolute numbers of involved nodes. Here we examine the data supporting the use of nodal ratios in breast cancer prognosis and consider the potential advantages and disadvantages of including nodal ratios in breast cancer staging. METHODS A systematic review of the literature was conducted using the following search engines: http://www.google.com; Thomsons ISI Web of Science; PubMed. RESULTS In multiple reports from both prospective and retrospectively collected data sets, nodal ratios have been shown to be significant predictors of outcome, including locoregional recurrence and overall survival. These studies span all stages of breast cancer and include various treatments as well as various statistical approaches. CONCLUSION There is considerable data supporting the use of nodal ratios in breast cancer prognosis. A thorough and methodological evaluation of the potential prognostic importance of nodal ratios in large multicenter data sets is merited and is currently being undertaken by the International Nodal Ratio Working Group.

Ratios of involved nodes in early breast cancer

IntroductionThe number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together.MethodsThe data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1–T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform.ResultsIn node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986–0.997) and 1.150 (1.058–1.249), respectively, but without improving R2N. In node-positive cases the hazard ratios were 1.003–1.088 for the number of involved nodes, 0.966–1.005 for the number of excised nodes, 1.015–1.017 for the percentage, and 1.344–1.381 for the log odds. R2N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios).DiscussionRatios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the number of nodes excised. In an extension to the study, ratios were validated in a comparison with categorized staging measures using blinded data from the San Jose–Monterey cancer registry. A ratio based prognostic index was also derived. It improved the Nottingham Prognostic Index without compromising on simplicity.

Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy

BackgroundOur aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up.MethodsFrom 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Blacks nuclear grade, type of surgery, and use of adjuvant therapy.ResultsOf 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%, 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence.ConclusionsMultidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT.