Stage Breast Cancer Patients Research Articles

Immunoglobulin G from Breast Cancer Patients in Stage I Stimulates Muscarinic Acetylcholine Receptors in MCF7 Cells and Induces Proliferation. Participation of Nitric Oxide Synthase-Derived Nitric Oxide

Muscarinic acetylcholine receptors (mAChR) belong to the G-protein-coupled receptor family and are extensively expressed in most cells in mammals. We had reported the expression of mAChR in murine and human breast tumors. The presence of antibodies in the sera of patients with different tumors directed against self-proteins has been recently described. In this work, we investigated the presence of autoantibodies against mAChR in the sera of breast cancer patients in stage I (T1N0Mx-IgG). IgG purification was performed by affinity chromatography in protein G-agarose. We also studied the ability of these antibodies to modulate the proliferation of MCF-7 breast tumor cells by the MTS colorimetric assay. The ability of T1N0Mx-IgG to stimulate muscarinic signaling pathway via nitric oxide synthase was tested by Griess reaction. We demonstrated M(3) and M(4) receptors expression in MCF-7 cells. T1N0Mx-IgG promotes cell proliferation, mimicking the action of the muscarinic agonist carbachol. This effect was preferentially due to M(3) receptor activation in tumor cells via phospholipase C-induced nitric oxide liberation by calcium-dependent nitric oxide synthases. IgG from control patients was unable to produce this effect. IgG from patients with breast cancer in early stages could be promoting tumor progression by muscarinic activation, and its presence could be determining the prognosis of this illness.

5160 Long-term prognostic effects of fasting insulin in early stage breast cancer (BC) patients

5160 Long-term prognostic effects of fasting insulin in early stage breast cancer (BC) patients

CCR5 and p53 codon 72 gene polymorphisms: Implications in breast cancer development

The aim of this study was to investigate the CCR5 gene and p53 codon 72 polymorphisms in a Brazilian population with breast cancer compared with healthy control subjects and to associate the clinical stage with these genotypes. No differences were detected for the D32 allele between breast cancer patients and the normal healthy donors (p=0.270), although this allele was more often present in blood donors. For p53 genotype analysis, breast cancer patients presented a significant (p<0.05) over-representation of p53 Arg homozygosity (55.5%) compared with the healthy control group (33.3%). Although no statistical difference occurred, a very strong tendency in breast cancer patients in stage III (p=0.0503) presenting homozygous genotype for Arg was verified. Five breast cancer patients were D32 deletion carriers and two patients presenting metastasis showed homozygous genotype for Arg. It is possible that p53 Arg homozygosity is associated with breast cancer and may represent a potential risk factor for breast tumorigenesis. In the present study, a higher percentage of breast cancer patients presented homozygous genotype for Arg and wild-type for CCR5 than the control subjects.

Preliminary safety results: addition of bevacizumab to 3 docetaxel regimens as adjuvant therapy for early stage breast cancer.

Abstract Abstract #4107 Background: Docetaxel-containing chemotherapy regimens improve disease-free survival (DFS) and overall survival in early stage breast cancer (BC) patients (pts). Bevacizumab (Bev) improves response rate and DFS in metastatic BC. This trial evaluates the feasibility of adding Bev to 3 adjuvant docetaxel BC regimens. Primary endpoint is cardiac safety (G3/4 congestive heart failure [CHF]).&amp;#x2028; Materials and Methods: Phase IIb, randomized, non-comparative study. Planned accrual: 225 pts (75/arm) with previously-untreated node-positive or high-risk node-negative BC. Eligibility: operable invasive adenocarcinoma ≥4 wks from surgery, normal cardiac function, known HER2 status. Pts with cardiac disease/risk of cardiac disease were not eligible. HER2 normal pts were randomized to (mg/m2 unless stated otherwise) Arm A (ACT): doxorubicin (A) 60 + cyclophosphamide (C) 600 q3w x 4 followed by docetaxel (T) 100 x 4 or Arm B (TAC): T 75 + A 50 + C 500 q3w x 6. FISH HER2+ pts received Arm C (TCH): T 75 + carboplatin AUC 6 q3w x 6 + trastuzumab (H) 6 mg/kg q3w x 52 wks. Bev 15 mg/kg q3w beginning Day 1 x 52 wks was administered in all arms. Granulocyte growth factor prophylaxis was mandated in all arms.&amp;#x2028; Results: Safety data are available for the first 138 pts (Arm A=53, Arm B=52, Arm C=33) receiving ≥4 cycles of treatment. Grade 3/4 toxicities (Arms A, B, C) included: neutropenia (n = 24, 22, 2), febrile neutropenia (5, 9, 0), leukopenia (10, 14, 1), thrombocytopenia (3, 7, 0) and fatigue (11, 3, 0). One on-study death occurred in Arm B from neutropenic enterocolitis. Documented CHF was reported in 3 pts (A=1, B=2), 2 occurring at the start of maintenance therapy. No cardiac events have been noted with Bev and H in Arm C. A total of 29 (21%) pts prematurely discontinued study treatment. Radiation therapy prior to study entry was administered in 4 pts (1, 1, 2). Concurrent Bev and adjuvant breast irradiation was administered in: Arm A=7 (13.2%), Arm B=15 (28.8%), Arm C=5 (15.2%). Most common AEs (Arms A, B, C) in these pts were: radiation skin injury (2, 2, 2), arthralgia (6, 4, 1), myalgia (4, 4, 1), bone pain (0, 4, 2), extremity pain (2, 1, 2), and rash (3, 3, 0).&amp;#x2028; Discussion: Preliminary data show an acceptable early safety profile, with no unexpected toxicity, when Bev was added to docetaxel adjuvant BC regimens. The addition of Bev did not result in increased risk of toxicity from standard radiotherapy administered either prior to or while on-study. Three early CHF events were observed; all occurred in pts receiving anthracyclines. No cardiac events have been identified with the Bev/trastuzumab combination. Accrual to the trial is ongoing. Updated results will be presented.&amp;#x2028; Support: sanofi-aventis,US. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4107.

Abstract 2545: Response to a preventive HER2/neu peptide (E75) vaccine based on HER2/neu status

Abstract Background: HER2/neu is a source of immunogenic peptides and is over-expressed in 30% of early stage breast cancer (BCa) patients. We have conducted clinical trials with the HER2/neu E75-peptide vaccine in node-positive and node-negative BCa patients demonstrating all levels of HER2/neu expression. Methods: A subset analysis review was performed of 165 BCa patients enrolled in our E75 vaccine trial based on the level of HER2/neu expression. Patients were HLA typed; HLA-A2+/A3+ patients were vaccinated (V); HLA-A2-/A3- patients served as controls (C). HER2/neu over-expressers (OE) were defined as FISH &amp;gt;2.0 and IHC 3+ HER2/neu tumors. Low-expressers (LE) included patients with IHC ranging from 0 to 2+. These 2 groups were assessed by clinicopathologic factors, immunologic response (in vivo DTH reactions and in vitro HLA-A2:IgG dimer assay) to the vaccine, and post-vaccine clinical responses (recurrence and survival). Results: Of 165 patients assessed; 94 were vaccinated (30 OE = 32%, 64 LE = 68%) and 71 were controls (22 OE = 31%, 49 LE = 69%). HER2/neu over-expressers were similar regarding prognostic and treatment factors, except a statistically larger number of V-OE patients were hormone receptor negative (ER/PR-; p=0.02) and node-negative (p=0.007). Clinicopathologic factors were not significantly different between control and V-LE patients. Immunologic responses were similar as measured by DTH reactions (post DTH V-OE=12.7+1.9 vs. V-LE=15.1+1.8; p=0.6), but V-OE demonstrated a decreased number of E75-specific CD8+ T cells when compared to V-LE post-vaccination (V-OE vs. V-LE Dimer: 0.6+0.06% vs. 0.8+0.07%; p=0.08; V-OE vs. V-LE Max Dimer: 1.5+0.1% 1.9+0.1%; p=0.04). At 30 months median follow-up, disease recurrence rates (RR) were similar between V-OE and C-OE patients (V-OE vs. C-OE RR: 4.3% vs. 5.6%; p=0.7); however there was a 50% reduction in mortality rate (MR) among patients that recurred (V-OE vs. C-OE MR: 25% vs. 50%; p=NS). RR was reduced for vaccinated patients with low HER2/neu expression (V-LE vs. C-LE RR: 6.4% vs. 11.3%; p=0.3). Importantly, MR among those that recurred was 0% vs. 38% (p=0.2) for V-LE and C-LE BCa patients, respectively. Conclusions: Patients with HER2/neu over-expressing breast cancer (FISH amplified (&amp;gt;2.0) and IHC 3+) respond well to the E75 vaccine immunologically and have a 50% absolute reduction in mortality compared to controls. Unexpectedly, patients with low-expressing (0 - 2+ on IHC) HER2/neu tumors show better response not only immunologically, but clinically with decreased breast cancer recurrence and 0% mortality following E75 peptide vaccination.

Expressão de caderinas e fator repressor em tumor de pacientes com câncer de mama na presença ou ausência de células malignas em medula óssea

OBJETIVO: Acredita-se que o perfil gênico do tumor é diferente daquele do tecido normal. Além disso, é possível que o tumor adquira características que lhe conferem potencial de gerar metástases em sítios específicos. A expressão tumoral de Caderinas 3 e 11 (envolvidas em adesão e migração celular), e de CBX3 (repressor transcricional) pode estar relacionada a maior agressividade e potencial invasivo em pacientes com câncer de mama (CM). Nosso objetivo é comparar a expressão de Caderina 3, Caderina 11 e CBX3 em tumor e tecido mamário normal adjacente e correlacionar a expressão tumoral destes genes com colonização da medula óssea (MO) por células tumorais. MÉTODOS: Amostras de tumor, tecido normal peritumoral e MO foram obtidas de 30 pacientes com CM estadio clínico I-III. A expressão de Caderina 3, Caderina 11 e CBX3 foi avaliada por RT-PCR em tempo real. A presença de células malignas em MO foi determinada por detecção da expressão de citoqueratina 19 por Nested-RT-PCR. RESULTADOS: Dezessete pacientes (56,7%) apresentaram células malignas em MO. Houve maior expressão de Caderina 3 e Caderina 11, mas não de CBX3 em tumor em relação ao tecido normal. Não encontramos associação entre expressão tumoral de Caderina 3, Caderina11 e CBX3 e a presença de células malignas em MO. CONCLUSÃO: A hiperexpressão de Caderina 3 e 11 em tumores em relação ao tecido normal sugere que estes transcritos possa mestar relacionados à carcinogênese. A expressão tumoral de Caderina 3, Caderina 11 e CBX3 não parece associada com a disseminação para a MO.

Phase I/II study of a 3 weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive (HER2+) early stage breast cancer (ESBC) patients (pt). GEICAM 2003–03 study

11032 Background: The liposome-encapsulated form of doxorubicin (Myocet™) (M) seems to be safe in terms of cardiotoxicity in combination with standard doses of trastuzumab (H) and paclitaxel in BC. This phase I/II study of M, H, docetaxel (T) and pegfligrastrim (N) was designed to evaluate the efficacy and safety of the combination, and define the MTD, in order to examine the selected regimen in a phase II trial. Methods: Cohorts of 3 HER2+ (FISH+) ESBC pt were treated at fixed dose of N (6 mg) and H (2 mg/kg/week). M and T were administered at the following dose levels (DL) (mg/m2): DL0, 60/75; DL-1, 55/75; DL-2, 50/70; DL-3, 50/65; DL-4, 50/60. The MTD was defined as &gt;1/6 pt in any cohort experiencing a predefined dose-limiting toxicity (DLT) in cycle (cy) 1 or 2. LVEF was assessed at baseline and every 2 cy. Results: Nineteen pt have been enrolled in phase I; all are evaluable for efficacy and toxicity. Median age was 45. Twelve pt (63%) were premenopausal. Median tumour size was 45 mm (20–80); 13 (68%) and 6 pt (32%) presented with stage II and IIIA BC respectively. Six (32%) of tumours were G3. DLT were G3 diarrhoea, febrile neutropenia, thrombocytopenia, infection, and G4 asthenia. Three additional pt were treated at DL-4 for confirmation of the recommended dose; none of them had a DLT. One pt (DL-2) experienced asymptomatic, reversible LVEF decrease to 49%. All pt have been assessed for pathological response: 6 (32%) and 5 pt (26%) achieved one pCR and one pPR in breast, defined as Miller and Payne score of 5 and 4, respectively. Conclusions: Concomitant administration of M plus THN is highly active regimen with manageable toxicity in pt with HER2+ ESBC tumours. DL-4 has been selected as the DL for the ongoing phase II study with an enrolment target of 59 pt. No significant financial relationships to disclose.

A Structural Model of the Relationships Between Perceived Control and Adaptation to Illness in Women with Breast Cancer

Objectives: To examine whether perceived control produces better adaptation to illness in breast cancer patients in stages I or II. Design: Longitudinal, 1-year following study. Methods: One hundred and one women were assessed on five occasions: one week after surgery, and again 1, 3, 6 and 12 months later, using, among other measures, the Mental Adjustment to Cancer (MAC) and the Hospital Anxiety and Depression Scale (HADS). Results: Structural equation models confirmed that patients with higher perceived control showed better adaptation to illness in all five assessments. Conclusions: These data fit well with previous research and suggest that psychological interventions which emphasize a sense of personal control would be effective in enhancing well-being in breast cancer patients at the early stages.

Expression of critical genes used as prognostic biomarkers and DNA damage in lymphocytes from breast cancer patients

10641 Breast cancer is the most common malignancy among women and its rate of mortality is still high. The increase knowledge of breast cancer biology is heaving great impact on determining the clinical prognosis and response to treatment. Impaired DNA repair may elevate the risk of malignant transformation of breast cells due to the accumulation of spontaneous mutations in target genes and increasing susceptibility to exogenous carcinogens. The present study was designed to evaluate the relationship between DNA damage and expression of some critical genes including TP53, c-ERBB2, ER (Estrogen Receptor) and PR (Progesterone Receptor) in breast cancer. Blood samples were obtained from female patients with diagnosed breast cancer before chemotherapy as well as from healthy individuals, and were processed in 24 hours. To evaluate the role of DNA repair in breast cancer we determined the level of DNA damage and the capacity to remove DNA damage induced by hydrogen peroxide in the peripheral blood lymphocytes. For this purpose the alkaline version of the comet assay, which provides a sensitive tool to investigate DNA damage and repair, was applied. The level of basal DNA damage was higher in breast cancer patients compared to the control group. Considerable inter-individual variations of DNA damage and repair in breast cancer patients were observed both before and after the treatment. The correlation between DNA damage in peripheral blood and expression of p53, c-erbB-2, PR and ER was analyzed. This preliminary study indicates that the DNA damage accumulation, observed in peripheral blood lymphocytes of breast cancer patients in early stages, could be attributed to impaired DNA repair. Our results suggest that DNA damage, as evaluated by the comet assay, seems to be useful molecular biomarker for monitoring ongoing exposures to DNA damaging agents. Such a research on the mutagen sensitivity and efficacy of DNA repair could impact on the development of new diagnostic and screening strategies. Work Supported by FAPERGS and GENOTOX (UFRGS). No significant financial relationships to disclose.

Evaluation of HER-2 in serum and tissue: correlation with clinical-pathological parameters and outcome in early stage breast cancer (BC) patients (pts)

20066 Background: HER2 is amplified and/or overexpressed in approximately 20–30% of invasive BC and is associated with poor prognosis. It is also a predictive marker of response to trastuzumab. The extracellular domain of the HER2 protein (sHER2) is frequently cleaved and released into the circulation where it can be detected by ELISA in up to 45% of advanced BC. We evaluated HER2 expression in paired serum and tissue samples of operable BC pts to analyze 1) the correlation between sHER2 and HER2 tumor status 2) their relationship with clinical-pathological parameters and 3) their impact on the outcome. Methods: 188 consecutive stage I-III BC pts were included in this study from May 2000 to July 2005. sHER2 was measured by ELISA (manual Kit “Oncogene Science Diagnostics” and automated version “ADVIA Centaur”) before the local treatment. Tumor tissue was analyzed by IHC with CB11 antibody and scored with Dako Hercept-test. HER2 amplification was determined using the Ventana FISH assay in patients with 2+ by IHC. Chi-squared test was used to evaluate the association between HER2 and patients’ clinical-pathological features. Survival outcomes were analyzed using Cox’s model. Results: Median age was 56.6 years; 122 pts received adjuvant chemotherapy, 54 endocrine therapy and 83 both. Forty-three pts (23%) had HER2 overexpression/amplification in tumor tissue and 25 pts (13%) had sHER2 levels ≥15 ng/ml (cut-off level) with a concordance of 85%. Both high sHER2 levels and HER2 tumor expression were associated with high histological grade (p = .02 and p &lt; .0001 respectively) and negativity of ER (p = .0035 and p &lt; .0001) and PgR (p = .0056 and p =. 002). At a median follow-up of 2.4 years we observed 8 deaths and 19 relapses. At univariate analysis high sHER2 levels (evaluated as continuous variable) were significantly correlated with shorter DFS (p = 0.0002) even if at multivariate analysis high sHER2 levels, after adjustment for stage and ER status, were associated with a shorter DFS with borderline significance (p = 0.06). Conclusion: Our preliminary data indicate that the evaluation of sHER2 at diagnosis defines a small subgroup of early BC pts with a poor prognosis even if it needs to be confirmed in a longer follow up. No significant financial relationships to disclose.

Circulating regulatory T cells in advanced breast cancer patients

10567 Background: It has been recently shown that regulatory CD4+CD25bright T cells (Tregs) are increased in patients with several malignancies and this increase correlates with advanced stage and dismal prognosis. Breast cancer (BC) patients represent a heterogeneous population with unpredictable natural history, even at advanced stages. We sought to monitor advanced stage (III and IV) BC patients, overexpressing HER-2/neu (HER) or not, for circulating Tregs before, during and after the administration of chemotherapy, either alone or in combination with Trastuzumab. Methods: Determination of circulating Tregs was performed in 50 μl whole peripheral blood by a Lyse NoWash FACS procedure and staining for CD45, CD4 and CD25. Tregs were determined as the lymphocytes expressing lower CD4 within the CD4+ T cell compartment and higher CD25 expression compared to the CD4 negative lymphocytes. Clinical evaluation of the patients was done according to RECIST criteria. Results: 24 HER+ and 19 HER- stage III / IV BC patients have been compared to 14 healthy donors, before therapy. The percentage of Tregs among the CD4+ T cell population of HER+ patients was significantly increased compared to both HER- patients and healthy donors (8,74 ± 2,68 vs 6,07 ± 1,85 and 6,55 ± 1,49, respectively). Trastuzumab combined with chemotherapy resulted in a progressive decrease in the percentage of circulating Tregs, reaching normal levels after the fourth cycle of treatment (6,95 ± 1,17). On a per patient basis, decrease in Tregs correlated either with documented partial response or stable disease, while increased Tregs during treatment coincided with progressive disease. No statistically significant change in the percentage of Tregs after chemotherapy was observed in HER- patients. Conclusions: 1) Increased Tregs do not directly correlate with clinical stage in BC, as stage III and IV HER (+) and (−) patients exhibit significantly different Tregs profiles. 2) HER+ advanced BC patients exhibit increased percentages of circulating Tregs and respond to the combination of Trastuzumab and chemotherapy by decreased Tregs. This decrease is either due to a reduction of the tumor burden or neutralization of circulating HER antigen by Trastuzumab, or a combination of both. No significant financial relationships to disclose.

Implications of Cancer Staging Uncertainties in Radiation Therapy Decisions

Radiation therapy (RT) for cancer is a critical medical procedure that occurs in a complex environment involving numerous health professionals, hardware, software, and equipment. Uncertainties and potential incidents can lead to inappropriate administration of radiation to patients, with sometimes catastrophic consequences such as premature death or appreciably impaired quality of life. The authors evaluate the impact of incorrectly staging (i.e., estimation of extent of cancer) breast cancer patients and resulting inappropriate treatment decisions. The authors employ analytic and simulation methods in an influence-diagram framework to estimate the probability of incorrect staging and treatment decisions. As inputs, they use a combination of literature information on the accuracy and precision of pathology and tests as well as expert judgment. Sensitivity and value-of-information analyses are conducted to identify important uncertainties. The authors find a small but nontrivial probability that breast cancer patients will be incorrectly staged and thus may be subjected to inappropriate treatment. Results are sensitive to a number of variables, and some routinely used tests for metastasis have very limited information value. This work has implications for the methods used in cancer staging, and the methods are generalizable for quantitative risk assessment of treatment errors.

P102 Cellular immunotherapy in late stage breast cancerpatients with reactivated autologous Memory T-cells derived from bone marrow

P102 Cellular immunotherapy in late stage breast cancerpatients with reactivated autologous Memory T-cells derived from bone marrow

Prognostic value of cell cycle regulator molecules in surgically resected stage I and II breast cancer

Success in breast cancer treatment depends greatly upon early detection, and in the employment of prognostic markers able to anticipate the evolution of the disease, allowing a more rational management of the patient. A fundamental cause of cancer is the alteration of the genetic material, which may modify the expression of proteins that play key roles in cell cycle progression. The aim of this study was to analyze the expression of cyclins D1, E, and B1 and of the CDKIs p16 and p21 in a population of uniformly treated patients with stage I or II breast tumors (n=56) compared with patients with benign breast pathology (n=23). Malignant breast tumors showed higher cyclin E and lower p21 expression than benign breast pathology (NS), determined by immunohistochemistry (IHC). In breast cancer patients, overexpression of cyclins D1 and E was associated with the presence of ER and stage respectively independently of other prognostic variables (multivariate analysis). Kaplan-Meier curves demonstrated that only overexpression of cyclin E was associated with a longer recurrence-free survival. Cox analysis showed that neither cyclins nor CDKIs were independent prognostic markers. We demonstrated that several regulators of cell cycle progression were altered in a large number of breast tumor cases, however, these abnormalities were not indicators of a worse outcome in breast cancer patients of stages I and II.

Regional nodal recurrence after conservative treatment for early stage breast cancer in patients with 1–3 positive axillary nodes

Regional nodal recurrence after conservative treatment for early stage breast cancer in patients with 1–3 positive axillary nodes

Regional nodal recurrence after conservative treatment for early stage breast cancer in patients with 1–3 positive axillary nodes

Regional nodal recurrence after conservative treatment for early stage breast cancer in patients with 1–3 positive axillary nodes

The role of growth factor support following neutropenic events in early stage breast cancer (BC) patients treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC): A sub-analysis of BCIRG 001

677 Background: TAC significantly improves disease-free and overall survival over FAC (HR 0.70, 0.68, respectively) and is emerging as one of the most active adjuvant treatments in patients (pts) with node positive early stage (BC) (Martin, SABCS 2003 #43). TAC is generally well tolerated but is associated with a higher incidence of febrile neutropenia (FN) vs FAC. ASCO clinical practice guidelines recommend secondary prophylaxis with G-CSF after FN in a prior cycle to maintain dose intensity. Methods: Pts with node-positive BC were randomized to TAC (75/50/500 mg/m2 q3wk x 6) or FAC (500/50/500 mg/m2 q3wk x 6). Corticosteroid premedication and prophylactic ciprofloxacin were given with TAC, but not with FAC. In case of FN (≥ gr 2 fever with gr 4 neutropenia), pts were treated with G-CSF for all subsequent cycles. This retrospective sub-group analysis compares the incidence of FN for cycles treated without and with G-CSF. Results: 1491 patients were accrued with 1480 evaluable for safety (TAC 744, FAC 736...

Frequency of axillary node dissection and chemotherapy in breast cancer patients over 60 years of age compared with those younger than 60 years of age

8161 Background: Axillary lymph node dissection (ALND) is used to stage breast cancer (BRCA) patients and to select appropriate adjuvant therapy. Older patients may not be offered ALND under the assumption they would not be candidates for chemotherapy. As a result, many patients over age 60 may be undertreated and have an increased risk of BRCA recurrence. The purpose of this study is to compare the rate of chemotherapy and ALND in patients older than 60 years with patients younger than 60 years. Methods: Retrospective chart review of invasive BRCA patients referred for adjuvant treatment at a single academic centre between January 1999 and March 2001. Demographic information, tumour characteristics, surgical and chemotherapy treatment data were collected. Co-morbidity was documented using the Charlson score which assigns 1–2 points for conditions including diabetes, angina, and vascular disease. Results: 293 patients less than 79 years of age were identified. In 166 patients under 60 years, 93.4% received node dissections, 69.3% received chemotherapy and 3.6% declined chemotherapy. However, of 127 patients between 60 and 79 years, 61.5% received axillary dissections, 29.1% received chemotherapy, and 9.5% declined chemotherapy. Average co-morbidity scores for patients less than 60 were 0.14, while those above 60 were slightly higher at 0.54. 7.2% of patients below age 60 had co-morbidities, in comparison 31.5% of those 60–79 had co-morbidities. Of those over 60 years with co-morbidity, the majority had only 1–2 health problems (80%). Tumour size (21 mm vs. 18 mm) and number of lymph nodes in those with ALND (1.1 vs. 0.8) were similar between groups. Conclusions: Although women aged 60–79 did not have a heavy burden of co-morbid illness; they were less likely to receive ALND or chemotherapy. Treatment decisions may be influenced by age rather than by co-morbid status or patient preference in those aged 60–79 who may otherwise be candidates for more aggressive treatment. No significant financial relationships to disclose.

Immunohistochemical analysis reveals a protective effect of H-ras expression mediated via apoptosis in node-negative breast cancer patients

Recently, we were able to demonstrate the favourable indication of H-ras expression in the clinically very important group of node-negative breast cancer patients. In order to further resolve a conceivable cellular effect mediated by the H-ras signal transduction pathway, we ascertained the apoptotic activity of the tumor cells of this overall 298 patients group. To this end, fragmented genomic DNA of breast cancer tissue was determined by specific DNA-end-labelling and subsequent visualization, thereby indicating early apoptosis induction. Tissues were considered apoptotic by means of the apoptotic index (quotient of apoptotic tumor cells and total tumor cells). One hundred and eighty-nine tumors (63.4%) were negative for apoptosis and 109 tissues (36.6%) were considered apoptotic (mean apoptotic index 11.9%, range, 0 to 90%). H-ras expression correlated significantly (chi2-test, p=0.004) to apoptosis. Furthermore, restricted to the node-negative subgroup, both H-ras expression and apoptosis were indicative of a better outcome (log-rank test p=0.0001, and p=0.012, respectively) during the observation time (median 87 months). These data suggest that H-ras expression effects the particular breast tumor cells by induction of apoptosis in breast cancer patients in an early stage without node involvement. The study indicates a possible mechanism, by which H-ras may act protectively.

Body Weight Loss as an Indicator of Breast Cancer Recurrence

Body weight loss (BWL), a major prognostic factor in breast cancer, was included as a parameter to be monitored in the recent breast cancer surveillance guidelines of the American Society of Clinical Oncology. The aim of this work was prospectively to evaluate BWL as an indicator of breast cancer recurrence. Body weight was measured every 2 months for 10.4 - 3.7 (SD) months in 109 disease-free breast cancer patients in stage II node-positive and stage III disease. The correlation between unexplained BWL and recurrence was studied. Attempts were made to define the limits in weight variations among disease-free patients beyond which recurrence could be suspected. Unexplained BWL was observed in 16/19 (84%) patients developing recurrence, versus 9 90 (10%) patients remaining disease-free. There was a significant (p < 0.001) correlation between BWL and recurrence. BWL anticipated the diagnosis of recurrence by 6 (range 4-12) months. Based on the average percentage weight variation - 2 SD (95% confidence interval) of the disease-free group, the limits for BWL beyond which recurrence could be suspected were a 5.8% decrease in the last 6 months, 3.6% in the last 2 months or 3.0% of the patient's mean weight. However, because of the large variation in the amplitude of individual weight oscillations among disease-free patients (from < 0.5% to > 5.9% of the mean weight), individual limits derived from the patient's own body weight curve seemed more reliable. The results suggest that unexplained BWL is a valuable indicator of incipient breast cancer recurrence. Careful monitoring of body weight in breast cancer patients during follow-up is encouraged.