Localized Breast Cancer Patients Research Articles

Baseline cognitive functions among elderly patients with localized breast cancer.

9510 Background: Cognitive deficits (CD) were reported among patients receiving chemotherapy (CT) for cancer, but could also be observed before treatment. Elderly patients were poorly studied although they are more prone to present age-related CD and CD onset or enhancement during CT. This study assessed baseline cognitive functions among elderly localized breast cancer (LBC) patients before adjuvant treatment therapy. Methods: Episodic memory, working memory, executive functions and information processing speed were assessed with neuropsychological tests. Validated questionnaires were used to assess subjective CD, anxiety, depression and fatigue before adjuvant treatment. Geriatric assessment was also realized. Objective CD were defined as a score less than 1.5 standard deviation (SD) of normative data on >2 tests, or less than two SDs on >1 test. Significant subjective CD (evaluated by the FACT-Cog) were defined when the 4 subscales below the first tercile distribution. Results: Results concern 123 elderly LBC (71±4 years): planned treatment included CT and radiotherapy (RT) for 61 patients and RT only for 62 patients. Characteristics are as follows: mastectomy (28%), stage (I: 60%, II: 27%, III: 13%), positive hormonal receptor (88%) and positive Her2 (17%). Before any adjuvant treatment, objective CD were observed in 40% of patients (46% in CT group, episodic memory mainly impaired and 37% in RT group, executive functions and information processing speed mainly impaired). No relation was observed between cancer stage, geriatric frailty and objective CD. Twenty nine percents of patients presented fatigue, 6% anxiety and 10% depression. These variables were not related to objective CD but they were related to subjective CD. Conclusions: More than 40% of elderly LBC patients presented objective CD before any adjuvant therapy that is higher than observed among younger patients. It is important to take account in the decision making of adjuvant treatment in elderly patients. Clinical trial information: NCT01333735.

Effect of chemotherapy on fatigue and presence of TNF- in breast cancer patients.

e20601 Background: Chemoterapy induced fatigue (CRF) is a common complain and few studies assessed so far the role of inflammatory biomarkers as predictors of CRF. OBJECTIVE: The primary objective of our study is to evaluate potential biomarkers of CRF in breast cancer (BC) patients receiving adjuvant Chemotherapy (CHT). Methods: Thirty-seven localized BC patients (clinical stages I-III) consecutively treated at the oncology service of Faculdade de Medicina da Fundação ABC were enrolled in this study. All patients received doxorubicin and cyclophosphamide based chemotherapy. Before the beginning of chemotherapy and before the second cycle, all patients answered the BFI (Brief Fatigue Inventory) questionnaire. The following inflammatory markers were collected: C-reactive protein (CRP), tumor necrosis Factor alpha (TNF-α) and interleukin 6 (IL-6). We correlated these inflammatory markers with BFI scores of each patient before and after cycle 1 and cycle 2 of chemotherapy. Results: The mean values of the inflammatory markers were: CRP 4.58 mg/dL (IC 95% 3.17-5.90), TNF-α 11 mg/dL ( IC 95% 8.84-13.79) and IL-6 3.74 (IC 95% 1.93-5.54). We observed a positive correlation between the BFI scores and TNF-α (p=0.0201). Conclusions: TNF-α may represent a potential CRF biomarker. Future studies may elucidate the potential usefulness of TNF-α for monitoring the anti-fatigue effects of new drugs for the treatment of CRF.

Abstract 1761: Extracellular telomeres can be detected in serum following cellular apoptosis in vitro and after chemotherapy in acute myelogenous leukemia (AML) patients.

Abstract Telomeres are repeated DNA sequences that cap the ends of each chromosome. Telomeres are temporally among the earliest genomic sequences to be degraded during apoptosis. We quantified telomeres in cell-free DNA (CF-DNA) in vitro and in vivo. CF-DNA was obtained by differential centrifugation of media or serum to remove intact cells and cellular debris. Telomere sequence in CF-DNA was measured with a quantitative PCR-based assay. We initially studied human breast cancer and brain cancer cell lines in vitro. We found that following treatment with doxorubicin, telomere sequences were rapidly detected in CF-DNA in the media (within 24-48 hours). We call these CF-DNA telomere sequences “extracellular telomeres” (ETs). ETs were preferentially secreted after chemotherapy. The telomere sequence molar fraction in the CF-DNA was up to 50,000-fold higher compared with other genomic sequences such as exons or structural DNA sequences such as alpha-satellite DNA. CF-DNA from the serum of 80 patients with a history of breast cancer and 40 normal female volunteers were analyzed. The patients with a history of metastatic breast cancer (n = 40) had 8-fold higher median value for ETs compared to those with a history of localized breast cancer (p=0.006). 20 normal women had ET levels similar to the local breast cancer patients. We thus hypothesized that the serum extracellular telomere assay could be used as a surrogate marker for in vivo apoptotic cell death. We collected sequential peripheral blood samples of newly diagnosed AML patients with a minimum peripheral circulating blast count of 2500/mm3 or more who received standard induction chemotherapy (anthracycline and cytarabine). These sequential peripheral blood samples were collected before, during and after standard chemotherapy at 12 hours interval for consecutive 21 days. The samples were immediately centrifuged to isolate CF DNA. Subsequently, ETs were quantitatively measured by qPCR telomere assay. In our preliminary data analysis of seven patients, we routinely observed two peaks of ETs about 10- fold higher than baseline that occurred about 2-3 and 4-6 days after initiating standard chemotherapy respectively. We conclude that 1) Telomere DNA is preferentially released from cancer cells in response to chemotherapy-induced apoptosis, 2) ETs can be detected and measured in normal patients and patients with a history of cancer, and 3) ETs are released after chemotherapy in AML patients. We are further investigating the relationship between ETs and other prognostic features in AML including initial white blood cell count, cytogenetics, disease free survival and overall survival. Citation Format: Amitkumar Mehta, Mallick Hossain, Christine Pressey, Johanna Tuomela, Varun Dhulipala, Sunil Rangarajan, Robert Crescentini, Arja Jukkola-Vuorinen, Katri Selander, David Graves, Kevin Harris, Uma Borate. Extracellular telomeres can be detected in serum following cellular apoptosis in vitro and after chemotherapy in acute myelogenous leukemia (AML) patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1761. doi:10.1158/1538-7445.AM2013-1761

Clinicopathologic Profile of Breast Cancer Patients in Pakistan: Ten Years Data of a Local Cancer Hospital

Breast cancer is the most frequent cancer of women worldwide, with considerable geographic and racial/ethnic variation. Data are generally derived from population based cancer registries in the developed countries but hospital data are the most reliable source in the developing countries. Ten years data from 1st Jan 2000 to 31st Dec 2009 of a cancer hospital in Pakistan were here analyzed by descriptive statistics to evaluate the clinicopathologic profile of local breast cancer patients. Among 28,740 cancer patients, 6,718 were registered as breast cancer. The female to male ratio was 100:2. Breast cancer accounted for 23% of all and 41% of female cancers. Some 46% were residents of Lahore, with a mean age of 47±12 years. Less than 1% were at Stage 0 and 10%, 32%, 35% and 23% were at Stage I, II, III and IV respectively. Histopathology was unknown in 4% while 91%, 2% and 1% had invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and mucinous carcinoma respectively. Rare carcinomas accounted for the rest. Tumor grade 1, 2 and 3 was 11%, 55% and 34% among the known. Profile of breast cancer patients in Pakistan follows a pattern similar to that of other developing countries with earlier peak age and advanced disease stage at presentation. The male breast cancer accounts for higher proportion in the local population. Local women have higher frequency of IDC and lower frequency of ILC and DCIS, owing probably to a different risk profile. Use of hospital information systems and establishment of population based cancer registry is required to have accurate and detailed local data. Promotion of breast health awareness and better health care system is required to decrease the burden of advanced disease.

P2-13-06: Feasibility of Fast-Track Germline Genetic Analyses for Localized Breast Cancer Patients and Its Impact on Local Management.

Abstract Background Patients with BRCA1-BRCA2 germline mutation who developed a first breast cancer (BC) have a high risk to develop a second BC, especially if aged less than 40 at first diagnosis. Thus, a positive BRCA test may influence the therapeutic management and orients towards non conservative surgery to reduce new BC occurrence. We set up a fast-track process to get BRCA1/2 and sometimes p53 mutation results within the shortest possible interval, in recently diagnosed BC patients whose probability to be mutation carriers was high (> 20%). Methods: Between 05/02/2009 and 03/01/2011, 61 patients diagnosed with localized BC requesting neo-adjuvant or adjuvant chemotherapy and whose personal or familial history fulfilled BRCA1/2 or P53 genetic testing criteria, were proposed genetic counselling. After a first multisciplinary team meeting (MT), genetic testing was proposed and performed according to usual genetic counselling rules. Psychological support was offered at every step of the process. Patients were informed that their test would be analysed as part of a fast-track process and were aware of the potential consequences of a positive test. Results were communicated and discussed during a second MT, when initial therapeutic plan was eventually changed. Results: All women who were referred to the genetic clinic for fasttrack testing accepted the analysis. The mean age at diagnosis was 38 (range 26–55). The whole process (from 1st genetic consultation till disclosure consultation) was completed in a median interval of 99 days (range 19–245). All pts received appointment within 5 days, when results were available. 50% pts postponed for more than 15 days their disclosure appointment (range 0–113 days). One patient (pt) declined result disclosure. 18 pts (30%) were found to be carrier of a deleterious mutation (13 BRCA1, 4 BRCA2, 1 p53). Variants of unknown significance (UV) in BRCA1 or BRCA2 genes were identified in another 4 patients. In 18 cases, surgery type initially proposed was changed because of the presence of the germline mutation: all pts were proposed ipsilateral mastectomy eventually associated to immediate reconstruction as often possible, as well as controlateral mastectomy. Final surgery turned to bilateral mastectomy in 3 patients with deleterious BRCA mutation and in one suspect UV 14 patients with mutation accepted the change, but four BRCA2 and one BRCA1 mutation carriers refused mastectomy or bilateral mastectomy. Radiotherapy was cancelled in a p53 mutation carrier. Conclusion: This data show that genetic testing might be considered as a part of therapeutic decision. Moreover, 22% (4/18) opted for a simultaneous controlateral prophylactic mastectomy. On the other hand, some women did not change their mind with mutation knowledge (4/18, 22%). Psychological impact of this procedure is currently retrospectively assessed by a self-questionnaire, fulfilled by mail. Analyses will be available for the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-06.

Estimating Decision-Relevant Comparative Effects Using Instrumental Variables

Instrumental variables methods (IV) are widely used in the health economics literature to adjust for hidden selection biases in observational studies when estimating treatment effects. Less attention has been paid in the applied literature to the proper use of IVs if treatment effects are heterogeneous across subjects. Such a heterogeneity in effects becomes an issue for IV estimators when individuals' self-selected choices of treatments are correlated with expected idiosyncratic gains or losses from treatments. We present an overview of the challenges that arise with IV estimators in the presence of effect heterogeneity and self-selection and compare conventional IV analysis with alternative approaches that use IVs to directly address these challenges. Using a Medicare sample of clinically localized breast cancer patients, we study the impact of breast-conserving surgery and radiation with mastectomy on 3-year survival rates. Our results reveal the traditional IV results may have masked important heterogeneity in treatment effects. In the context of these results, we discuss the advantages and limitations of conventional and alternative IV methods in estimating mean treatment-effect parameters, the role of heterogeneity in comparative effectiveness research and the implications for diffusion of technology.

Correlation between change of serum HER2/neu before and after neoadjuvant chemotherapy and clinical outcomes in advanced breast cancers.

e21067 Background: We searched for correlation between the response of advanced breast cancers in neoadjuvant chemotherapy and the change of serum HER2/neu, and short term disease free survival. Methods: 22 localized advanced breast cancer patients were treated by neoadjuvant chemotherapy (adriamycin: 17, trastuzumab: 5). We concerned HER2/neu positive breast cancer when IHC3+ or FISH amplified. Serum HER2/neu levels were measured by chemiluminescence immunoassay (ADVIA centaurTM system) before neoadjuvant chemotherapy and before operation. The cutoff value was 10.2 mg/ml according to previous study. We considered clinical outcomes as short term disease free survival and disease free interval for investigating of the role of serum HER2/neu in a prediction of clinical outcomes. Results: Mean of serum HER2/neu before chemotherapy was 15.8± 1.6ng/ml, and that after chemotherapy was 10.6 ± 0.38ng/ml. Partial response (PR) was 17 patients and complete response (CR) was 5 patients. Mean of change in serum HER2/neu was 5.1± 2.1ng/ml, and change of serum HER2/neu in CR group was higher than PR group (13.26 ± 14.1ng/ml; 2.74±3.2ng/ml,p=0.008). Change of serum HER2/neu in trastuzumab group was higher than that in adriamycin group (12.8±14.5ng/ml; 2.8±3.2ng/ml, p=0.012). In adriamycin group, CR was not correlated with change of serum HER-2/neu (PR: 3.03±3.3NG/ML; CR: 1.65±1.62ng/ml, p=0.58). In trastuzumab group, it also was not correlated (PR: 0.6 ±1.13ng/ml; CR: 21.0 ±13.2ng/ml, p=0.083). CR was correlated with change of serum HER2/neu, initial serum HER2/neu, and treatment group (T>A, p=0.024). Mean follow up duration was 41months, the change of serum HER2/neu before and after chemotherapy was not correlated with disease recurrence (NED: 8.6± 11.4ng/ml, REC: 2.1± 0.65ng/ml, p=0.082). The change of serum HER2/neu was not correlated with disease free interval (p=0.07). Conclusions: The change in serum HER2/neu was associated with pathologic response with neoadjuvant chemotherapy, but not specific in the chemoregimen. The bigger change of serum HER2/neu, the better prognosis was estimated, even a limited study, but it needs further studies.

One-Year Longitudinal Study of Fatigue, Cognitive Functions, and Quality of Life After Adjuvant Radiotherapy for Breast Cancer

Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life. Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules. At baseline, 60% of the CT-RT patients expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment. Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.

Use of metabolic profiling by metabolomic technology to distinguish between localized and metastatic breast cancer patients.

e21005 Background: Tumor pathophysiological conditions depending on tumor cell metabolism and tumor microenvironment offer an opportunity to better characterize tumors by providing metabolic signature. Metabolomics is the combination of analytical techniques such as Nuclear Magnetic Resonance (NMR) spectroscopy with statistical data analysis methods aimed to evaluate the metabolic status of biofluids. This technology may be relevant for breast cancer prognosis. Therefore, the first objective of this study was to provide evidence that metabolomics from patients' (pts) blood sample is able to distinguish between metastatic and localized breast cancer. Methods: Serum samples from 2 cohorts of pts were analyzed using 1H NMR spectroscopy on a Bruker Avance III spectrometer operating at 800 MHz and equipped with a triple resonances automated TXI probe. Fasting blood sample were drawn from 30 pts with localized breast cancer (before surgery), and from 25 pts with metastatic breast cancer (before the first chemotherapy injection). For each sample, a 1D NMR spectrum was acquired, showing a large number of resonances corresponding to protons belonging to different classes of metabolites. A spectral database was generated, and bioinformatic tools were used to analyze the results using supervised multivariate analysis (Partial Least Square Regression). Results: The use of very high-field NMR allows the acquisition of resolved spectra with a reliable assignment of resonances based on multidimensional homo- and heteronuclear experiments. We identify metabolic signature of metastatic breast cancer, which is statistically different from the metabolic signature of localized breast cancer. Target analysis is on going to have further quantitative analysis of a class of metabolites that are related to the metastatic condition. Conclusions: Metabolomics may become a novel biomarker for cancer prognosis. Prospective studies to validate metabolomics as a prognostic/predictive tool are planed. No significant financial relationships to disclose.

A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients

To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients. From May 2004 till October 2007, 340 patients with stage II and III breast adenocarcinoma, ineligible for breast conserving surgery, received eight sequential three weekly cycles of EC-D [epirubicin (75 mg/m(2))-cyclophosphamide (750 mg/m(2)) for four cycles followed by docetaxel (100 mg/m(2)) for four cycles]. HER2-negative patients (N = 220) were randomized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5-8 or no additional treatment, while HER2-positive patients confirmed by FISH (N = 120) were randomized to trastuzumab concomitant to docetaxel (8 mg/kg then 6 mg/kg IV every 3 weeks) or no additional preoperative treatment. In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5 and 13% of patients treated without and with neoadjuvant Celecoxib, respectively. In the HER2 positive group, pCR rate reached 26% in those who received neoadjuvant trastuzumab versus 19% in the others. There was no unexpected toxicity, no cardiac toxicity, and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%. Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor. In HER2-positive tumor patients, trastuzumab added to ECD leads to increased pCR rates. It was the only combination to deserve further study according to the two-stage Fleming's design used in this trial.

Adjuvant Chemotherapy for Early Breast Cancer in the Elderly

The use of cytotoxic therapy in the fit elderly breast cancer patient has been tempered with concerns of age, physical function, and co-morbid illness. In the appropriate patient with biologically aggressive disease, such as receptor poor breast cancer, it is reasonable to consider combination chemotherapy as part of an adjuvant program. If this approach is to be employed, the physician must also consider the patient's co-morbid conditions and status of function in society as potential indicators of toxicity or lack of benefit. In this case, a formal geriatric assessment is of value. A Cancer and Leukemia Group B (CALGB) trial of monotherapy vs combination cytotoxic therapy as adjuvant treatment for localized breast cancer patients over 65 years of age has determined that the combination approach is superior to single agent therapy. In an unplanned analysis of receptor rich and receptor poor tumors, the patients with receptor poor tumors seemed to achieve the greatest benefit from combination cytotoxic therapy. Adjuvant chemotherapy can also be considered for patients with high-risk receptor rich breast cancers. However, the use of chemotherapy in the elderly patient with breast cancer is largely based upon data emerging from trials in younger patients. Studies specifically for patients over 65 years of age are urgently needed in this population to provide evidence-based proof of the current approach.

Flow cytometric assessment of monocyte activation markers and circulating endothelial cells in patients with localized or metastatic breast cancer

Monocyte activation in cancer patients may be reflective of anticancer activity. However, studies indicate that recruitment of macrophages can actually promote tumor growth and angiogenesis. Assessment of other microenvironmental cells such as circulating endothelial cells (CECs) may provide additional information regarding disease progression. The objective of this study was to assess monocyte activation and CECs in breast cancer patients and determine the potential clinical relevance during disease progression. Patients (n = 41) with localized or metastatic breast cancer who were not currently receiving treatment were eligible for study inclusion. Peripheral blood was collected and analyzed by flow cytometry for monocyte activation (Leuko64 assay kit), and for CECs (CD146(+)CD45(-) phenotype). Metastatic breast cancer patients demonstrated a higher monocyte CD64 index relative to normal donors and localized breast cancer patients (P < 0.05). Furthermore, breast cancer patients had a lower monocyte CD163 index relative to normal donors (P = 0.008). Localized breast cancer patients demonstrated higher levels of CD146(+)CD45(-) cells CECs relative to metastatic breast cancer patients and normal donors. Within the localized breast cancer population, levels of CD146(+)CD45(-) cells increased with disease stage (P < 0.05). These results suggest that monocyte activation and CECs may play a role in breast cancer progression. We speculate that monocyte activation may reflect a reaction to metastatic cells and/or response to tissue damage caused by metastatic growth in distant organs. Furthermore, the observation that CECs increase with disease stage in localized breast cancer suggests that CECs could be a useful surrogate marker for disease progression in this patient population.

Prognostic role of epidermal growth factor receptor in localized breast cancer: 15 Years of follow-up

Background: The expression of epidermal growth factor receptor (EGF-R) in breast cancer (BC) is generally considered as an unfavorable event during tumor progression. Its predictive role has been fairly well defined: EGF-R expression predicts tamoxifen unresponsiveness. EGF-R role in autocrine growth regulation was confirmed. However, reported results on its prognostic role in BC patients were conflicting. The prognostic role of EGF-R after 15 years of follow-up is analyzed in a group of 70 localized BC patients, presented at diagnosis in clinical stages I-III. Methods: BC patients newly diagnosed from December 1990 until March 1991, treated in accordance to the National Protocol, were selected for EGF-R analysis. Steroid receptors and EGF-R were determined at diagnosis in same frozen tissue samples, using biochemical methods. Except 6 patients who were lost from follow-up in the interval shorter than 60 months, the remaining patients were followed-up from 60-188 months. The total number of events was 32 relapses (46%), and 27 deaths (38.5%). Results: EGF-R expression was found in 28/70 patients (40%), and the EGF-R content higher than 26 fmol - in 15/70 patients (21%). Neither the expression, nor the high content of EGF-R showed any influence on disease-free or overall survival. Levels of EGF-R were similar in relapsing and relapse-free patients. Nodal status had the strongest infuence on prognosis. Conclusion: Our results suggest that the controversial findings, regarding the EGF-R prognostic role, might be the consequence of a genuine weak influence of EGF-R expression on disease outcome. .

Persistence of occult metastatic cells in bone marrow after adjuvant systemic therapy predicts relapse in localized breast cancer

657 Background: The presence of isolated tumor cells (ITC) in bone marrow (BM) in breast cancer patients has been evaluated in numerous studies. The majority of these studies have found correlation between the presence of ITC in BM and increased risk of relapse. In this study we assessed the association between the presence of BM and established prognostic factors in localizated breast cancer patients, and analyzed the influence of adjuvant therapies on the remove of these cells as a prognostic factor. Methods: BM aspirates from 296 patients with primary breast cancer with stages I-III (112 node negative, and 184 node positive), treated with adjuvant systemic chemotherapy (CT) with antracyclines, were evaluated. All patients underwent BM aspirate at diagnosis. In addition, 202 of these patients also underwent a second BM aspirate after CT. Carcinoma cells were detected using a standardized immunoassay with monoclonal antibody A45-B/B3 directed against cytokeratin. Detection of >= 2 tumor cells was scored as positive. Results: At diagnosis, 82 of 296 (28%) patients presented ITC in BM. The presence of ITC in BM did no correlate with standard prognostic variables such as lymph node status, tumor size, histological grade, hormonal receptor levels and expression of HER-2 neu. After a median follow up of 35 months (6–130), 53 patients (18%) relapsed (10 node negative, and 43 node positive). In the global group, the presence of ITC in BM at diagnosis showed a tendency to predict worse disease-free survival (DFS) and overall survival (OS). In the lymph node-positive group, 62% of patient showing ITC in the second BM aspirate after CT relapsed, whereas 21% of those with both negative BM aspirates presented relapse. The presence of ITC in the second BM aspirate was associated with inferior DFS (P=0,01) and OS (p=0,002). Conclusions: Our analytical approach allows the identification of micrometastatic BM disease in localized breast cancer patients that would be usually undetected using conventional methods. The persistence of occult metastatic cells in BM after adjuvant systemic therapy predicts relapse in localized breast cancer. No significant financial relationships to disclose.

Analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy

Purpose : Hematopoiesis is among the most sensitive systems in the body to radiation. Routine complete blood counts (CBCs) are common in clinical radiotherapy practice. Only a few studies have attempted to characterize the behavior of peripheral blood levels during partial body radiation therapy with field sizes smaller than those used in hemibody or total nodal irradiation. Such information is needed to identify which patients are at risk for cytopenia and require close monitoring. Methods and Materials : In 1993, 412 new patients were seen at Michael Reese Hospital for radiotherapy. A total of 972 weekly CBCs were identified for 155 patients receiving a minimum of 5 weeks of treatment for breast, prostate, lung, gynecological, or head and neck malignancies. Linear regression models were fitted to the weekly CBC values for those patients who had pretreatment CBC values recorded. Factors affecting starting levels, rates of decline, and nadirs during treatment were determined for leukocytes, platelets, and hemoglobin. Results : Leukocytes declined most dramatically during the first week of treatment (16% from pretreament to Week 1 levels) and then at a rate of 3.3% per week from Week 1 to Week 7 ( p < 0.0010. Total mean leukocyte decrease over 7 weeks of therapy was 30%. Platelets declined 9% on average during the first week of therapy and then at a mean rate of 1.4% per week ( p < 0.02). A statistically significant decrease in hemoglobin levels could not be detected. No difference in the rate of decrease could be found for different disease sites, age groups, or amount of marrow irradiated. The effects of chemotherapy were variable, depending on blood element and whether therapy was sequential or concomitant. The odds of a nadir <2000 counts/mm 3 for white blood count (WBC), <50,000 counts/mm 3 for platelets, and <8.0 g/dl for hemoglobin were all well below 5%. A strong correlation existed between starting CBC values and nadirs; patients with lower Week 1 CBC levels were most likely to have the lowest nadirs. Conclusions : Low CBC levels during radiation therapy are likely to be the result of other medical problems that cancer patients face. Regional irradiation with small field sizes (<40% of total body marrow) typically used in clinical radiotherapy is unlikely to be the cause of marrow depression significant enough to warrant medical intervention. Blood levels taken during the first week of treatment (Week 1) can be used to determine risks of developing critical nadirs. Localized breask and prostate cancer patients are unlikely to require routine CBCs if initial levels are normal. Routine CBC levels on all radiation oncology patients without other reasons for hematopoietic depression requires reevaluation, as millions of dollars are spent on unnecessary testing. If weekly CBC blood levels are avoided in localized breast and prostate cancer patients, this alone could potentially result in a savings of as much as $40 million a year nationally.

Survival from Localized Breast Cancer: Variability Across Trials and Registries

Age-specific (< 50, 50-69 years) 10-year survival proportions in four European trials for node-negative, Stage I and II breast cancer patients differ significantly. These patients, identified as having the same stage as localized-breast cancer patients in the End Results Registry of the U.S. National Cancer Institute, had pooled survival proportions for the two age groups (0.713, 0.579) close to those of the registry (0.713, 0.607).