Chemotherapy For Early-stage Breast Cancer Research Articles

A randomized, multi-center, open-label, phase II study of once-per-cycle DA-3031, a biosimilar pegylated G-CSF, compared with daily filgrastim in patients receiving TAC chemotherapy for early-stage breast cancer

A pegylated form of recombinant granulocyte-colony stimulating factor (G-CSF) was developed for prophylactic use in breast cancer. The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer. A total of 61 patients receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were randomized in cycle 1 to receive daily injections of filgrastim (100 μg/m(2)) or a single subcutaneous injection of pegylated filgrastim DA-3031 at a dose of either 3.6 mg or 6 mg. The mean duration of grade 4 neutropenia in cycle 1 was comparable among the treatment groups (2.48, 2.20, and 2.05 days for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.275). No statistically significant differences were observed in the incidence of febrile neutropenia between the treatment groups (9.5 %, 15.0 %, and 5.0 % for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.681) in cycle 1. The incidences of adverse events attributable to G-CSF were similar among the treatment groups. Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.

Association of osteprotegerin, bone turnover, and bone loss after adjuvant chemotherapy in early-stage breast cancer.

134 Background: Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. RANK-RANK ligand (RANK-L) signaling is important in regulating osteoclast development and is essential in maintaining the balance between bone resorption and formation. Osteoprotegerin (OPG) is involved in RANK-RANKL signaling by acting as a decoy receptor for RANK and thus interrupting osteoclast activation and subsequent bone resorption. The objective of this study was to examine the relationship between OPG and bone health in women with early-stage breast cancer who develop CIOF. Methods: Premenopausal women with stage I and II breast cancers receiving adjuvant chemotherapy were evaluated, within 4 weeks of starting chemotherapy (baseline), at 6 months and at 12 months. They were evaluated with bone mineral density (BMD) at lumbar spine (LS), BMD at femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium (iCa), osteocalcin (OC) and osteoprotegerin (OPG) measurements. CIOF was defined as negative pregnancy test, 3 or more months of amenorrhea, and an FSH >30 MIU/mL at the 12 month time point. Results: Forty women with stage I and II breast cancer receiving adjuvant were included in this analysis. Thirty-one (77.5%) were identified as having CIOF. In the CIOF group, there was statistically significant decreases in BMD (at the LS and FN) at both 6 months and 12 months (all P's <0.001). The LS BMD decreased from 0.993 (0.935-1.123), to 0.976 (0.869-1.100) to 0.937 (0.834-1.062), at 6 and 12 months respectively (median and inter-quartile range). OPG was significantly increased at 6 months (median increase 0.30, P=0.015), and then went down at 12 months, but was still higher than baseline (although not statistically significant, median difference 0.2, p=0.70). Significant increases in OC were also noted at 6 and 12 months (both P<0.001). Conclusions: In the CIOF group, OPG increases in the first 6 months in CIOF and at 12 months was slightly decreased but still remained elevated over baseline. This is likely due to a compensatory response to rapid bone loss. This compensatory response has been reported in other diseases, but not in CIOF.

Full-dose chemotherapy in early stage breast cancer regardless of absolute neutrophil count and without G-CSF does not increase chemotherapy-induced febrile neutropenia

Does giving full-dose adjuvant chemotherapy to patients with early stage breast cancer (ESBC) regardless of the day-before absolute neutrophil count (ANC) lead to an increased incidence of chemotherapy-induced febrile neutropenia (CIFN)? What factors may predispose patients to CIFN? This was a retrospective chart review conducted on all patients receiving adjuvant chemotherapy for ESBC at a mid-sized community hospital in Toronto, Ontario, Canada between September 2005 and August 2011. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. One hundred fifty-four patients met the inclusion criteria. Overall, 830 cycles of chemotherapy were analyzed. Univariate and multivariate logistic regression analyses were used to identify risk factors for CIFN. Twenty-two episodes of CIFN were observed. There was no significant difference in day-before ANC between patients who developed CIFN relative to those who did not. The day-before ANC was <1.5 × 10(9)/L for 88 cycles of chemotherapy. ANC analyzed as a continuous variable showed that the odds ratio (OR) for CIFN was 0.97 (95 % CI 0.82-1.13, p = NS). The pseudo R (2) statistic, which is a measure of variability accounted for by a regression model, was only 0.0008, indicating that ANC explained less than 1 % of the variability in the risk of CIFN. The most significant predictor of CIFN was the chemotherapy regimen, with docetaxel (Taxotere)/cyclophosphamide demonstrating the highest risk (OR 7.1, 95 % CI 1.4-34.9, p = 0.016). Full-dose adjuvant chemotherapy may be given to patients with ESBC regardless of the day-before ANC, without significantly increasing the risk of CIFN. The chemotherapy regimen is the most significant predictor for CIFN.

Abstract P1-15-04: The relationship of relative dose intensity and supportive care to febrile neutropenia rates in patients with early stage breast cancer receiving chemotherapy: a prospective cohort study of chemotherapy-associated toxicity

Abstract Background: Febrile neutropenia (FN) represents a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. Patients have the highest risk of the initial neutropenic event in cycle 1 when most patients receive full dose chemotherapy. This study evaluates time course of neutropenic events in patients receiving chemotherapy for early-stage breast cancer (ESBC) and supportive care interventions that modify FN risk in ESBC patients treated in actual oncology practice. Methods: A prospective cohort study of adult cancer patients with solid tumors or lymphoma starting a chemotherapy regimen was conducted at 115 U.S. sites. Toxicities associated with chemotherapy were recorded in up to 4 cycles including severe neutropenia (SN), FN, and infection. Documented clinical interventions included reductions in chemotherapy relative dose intensity (RDI), the use of colony-stimulating factors (CSFs), and antibiotics. Results: A total of 1202 ESBC patients starting chemotherapy were analyzed, of which 1154, 1099, and 896 reached the midcycle of cycles 2, 3, and 4, respectively. While the majority of neutropenic and infection events occurred in cycle 1, decreasing rates of FN and infection in later cycles correlated with increasing reductions in dose intensity and increased use of CSFs and antibiotics. The overall risk of FN in all patients combined was 16.3 %. It reached 21.1% for patients who started with planned RDI≥85% and without primary CSF prophylaxis. There was no significant difference in FN rates by menopausal status or hormone receptors. Conclusions: While the risk of neutropenic complications is highest during the first cycle of chemotherapy, reductions in neutropenic events during subsequent cycles are associated with reduced chemotherapy dose intensity or increased use of supportive care measures. Nevertheless, the cumulative risk of neutropenic events remains high in ESBC patients receiving full dose chemotherapy without prophylactic measures overall and across menopausal and hormone receptor subgroups. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-04.

Re: Clinical Validity/Utility, Change in Practice Patterns, and Economic Implications of Risk Stratifiers to Predict Outcomes for Early-Stage Breast Cancer: A Systematic Review

BACKGROUND At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers. METHODS A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported. RESULTS Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications. CONCLUSION The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.

Adjuvant chemotherapy for early-stage breast cancer: Choice of regimen and associated hematologic toxicities in a metropolitan Australian hospital.

123 Background: The commonly used adjuvant chemotherapy regimens for early breast cancer include 5-fluorouracil, epirubicin, cyclophosphamide and docetaxel (FEC-D), docetaxel and cyclophosphamide (TC), doxorubicin and cyclophosphamide with or without paclitaxel and/or herceptin (AC combination) and docetaxel, carboplatin and trastuzumab (TCH). Hematologic toxicity from these regimens can be life threatening as well as cause significant morbidity for the patient and major costs to the health system. Granulocyte colony stimulating factor (GCSF) is frequently used to try and reduce these complications. In Australia, GCSF is funded for use as primary prophylaxis with docetaxel in combination with an anthracycline and cyclophosphamide. Secondary prophylaxis is available only after demonstration of prolonged severe neutropenia or an episode of febrile neutropenia (FN). Methods: Patients treated with adjuvant chemotherapy for early breast cancer at Gold Coast Hospital, Qld, Australia from February 2010 to February 2012 were identified. Patient charts were reviewed for incidence of neutropenia (neutrophil count &lt;1.0 x 109/L), FN (temp ≥38°C), dose reductions or delays and use of GCSF. Results: 102 patients were treated over this time. Incidence of neutropenia, FN and use of GCSF are summarised below. 30 patients receiving FEC-D had a dose delay or reduction with the majority due to non-haematologic toxicities. 96% patients completed 6 cycles of treatment. Of the patients with FN in the TC group, half had received primary GCSF. No patients who were given primary GCSF experienced a dose delay. Similar trends were observed in the other treatment groups. Conclusions: Our results show that patients receiving FEC-D along with GCSF had lower rates of neutropenia and hospitalisations. Rates of neutropenia and dose delay are higher in the other groups. FEC-D is the most commonly used regimen in our institution likely due to the availability of GCSF. [Table: see text]

Cost-effectiveness of the 21-gene recurrence score assay in the context of multifactorial decision making to guide chemotherapy for early-stage breast cancer.

New evidence is available regarding the utility of the 21-gene recurrence score assay in guiding chemotherapy use for node-negative, estrogen receptor-positive breast cancer. We applied this evidence in a decision-analytic model to re-evaluate the cost-effectiveness of the assay. We cross-classified patients by clinicopathologic characteristics from the Adjuvant! risk index and by recurrence score risk group. For non-recurrence score-guided treatment, we assumed patients receiving hormonal therapy alone had low-risk characteristics and patients receiving chemotherapy and hormonal therapy had higher-risk characteristics. For recurrence score-guided treatment, we assigned chemotherapy probabilities conditional on recurrence score risk group and clinicopathologic characteristics. An estimated 40.4% of patients in the recurrence score-guided strategy and 47.3% in the non-recurrence score-guided strategy were expected to receive chemotherapy. The incremental gain in quality-adjusted life-years was 0.16 (95% confidence interval, 0.08-0.28) with the recurrence score-guided strategy. Lifetime medical costs to the health system were $2,692 ($1,546-$3,821) higher with the recurrence score-guided strategy, for an incremental cost-effectiveness ratio of $16,677/quality-adjusted life-year ($7,613-$37,219). From a societal perspective, the incremental cost-effectiveness was $10,788/quality-adjusted life-year ($6,840-$30,265). The findings provide supportive evidence for the economic value of the 21-gene recurrence score assay in node-negative, estrogen receptor-positive breast cancer.

Effect of obesity on toxicity in women treated with adjuvant chemotherapy for early-stage breast cancer: a systematic review

The purpose of this study is to provide more definite evidence regarding the role of dose modification of chemotherapy in obese women with breast cancer by systematically reviewing current literature regarding chemotherapy-induced toxicity rates in obese and non-obese women with early-stage breast cancer. A systematic search of Pubmed and EMBASE was conducted to identify original studies investigating chemotherapy-induced toxicity in obese women receiving adjuvant chemotherapy treatment for breast cancer. Ten studies were identified. We noted low rates of adjustment for confounders such as prophylactic hematopoietic growth factor use and empirical dose reductions. Seven studies found reduced toxicity in obese compared to non-obese women. Of four studies, where dose capping was precluded or statistically adjusted for, three found reduced toxicity in obese women. These outcomes include less febrile neutropenia (body mass index (BMI) >23.6; odds ratio (OR) 4.4; 95 % confidence interval (CI) 1.65-12.01), fewer hospital admissions (BMI >35; OR 0.61, 95 % CI 0.38-0.97), and fewer neutropenic events (BMI >25; OR 0.49; 95 % CI 0.37-0.66). Only a single study reported higher rates of toxicity in obese women, but this study had significant methodological issues. As a conclusion, we observed that obese patients tolerate chemotherapy better than lean patients. However, this may be confounded by poorly specified dose capping practices and the use of hematopoietic growth factors. Further research should focus on improved documentation of body size, of dose, and of use of growth factors, and analysis of how these affect recurrence rates, toxicity, and survival.

Clinical Validity/Utility, Change in Practice Patterns, and Economic Implications of Risk Stratifiers to Predict Outcomes for Early-Stage Breast Cancer: A Systematic Review

At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers. A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported. Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications. The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.

Cost-effectiveness of the 21-gene recurrence score assay in the setting of multifactorial decision making for chemotherapy in early-stage breast cancer.

1525 Background: The objective of this study was to incorporate evidence from two recently-published studies to reevaluate the cost-effectiveness of the 21-gene Recurrence Score (RS) assay (Oncotype DX) in the context of multifactorial decision making to guide the use of chemotherapy for node-negative, estrogen receptor–positive breast cancer in the United States from the societal and healthcare system perspectives. Methods: We developed a decision-analytic model to first cross-classify hypothetical patients by clinicopathologic characteristics according to the Adjuvant! using risk groups and RS risk groups. We generated estimates of long-term costs, survival, and quality-adjusted survival for the RS-guided and non–RS-guided strategies using a probabilistic state transition model. In addition to costs for the 21-gene assay, we assigned attributable costs for chemotherapy, hormonal therapy, monitoring for disease recurrence, and distant recurrence. For the societal perspective, we also considered incremental patient time costs. Costs and survival were discounted at 3% annually. Results: With the RS-guided strategy, 40.4% of patients were expected to receive chemotherapy relative to 47.3% in the non–RS-guided strategy. Targeted use of chemotherapy in the RS-guided strategy was expected to increase survival by 0.19 years (95% CI, 0.09 to 0.32) and 0.16 QALYs (95% CI, 0.08 to 0.28). Lifetime direct medical costs were expected to be $2692 (95% CI, 1546 to 3821) higher with the RS-guided strategy. The incremental cost-effectiveness ratios (ICERs) were $14,059 per life-year saved (95% CI, $6840-$28,912) and $16,677 per QALY (95% CI, $7613-$37,219). When incorporating lower indirect costs of $950 per patient, the ICERs were $9095 per life-year saved (95% CI, dominant-$23,397) and $10,788 per QALY (95% CI, $6840-$30,265). In probabilistic sensitivity analysis, more than 99% of the ICERs were less than $50,000 per life-year saved and per QALY. Conclusions: Our updated cost-effectiveness estimates are supportive of the economic value of the 21-gene RS assay in the setting of node-negative, estrogen receptor–positive breast cancer.

Abstract 2654: A prospective study of the effects of adjuvant chemotherapy (CT) on cognition and brain function in breast cancer patients

Abstract There is an accumulating body of literature reporting that cognitive deficits, possibly long lasting, including lack of concentration, short-term memory loss and difficulties in multitasking are observed in patients receiving chemotherapy (CT) (“chemobrain”). We have used functional magnetic resonance imaging (fMRI) to determine the nature of the changes in brain function that underlie the cognitive deficits that can result from CT. This research was carried out prospectively in women being treated with adjuvant CT for early-stage breast cancer (BC). Methods: Seven healthy aged-matched control subjects (No CT) and six subjects with BC took part in this study undergoing functional fMRI scanning on a 3.0T scanner prior to initiating CT and after receiving their fourth cycle of anthracycline-based CT. Task activation (n-back) and resting-state functional connectivity (fC) scans were carried out. The N-back letter task is a continuous performance task having 3 levels of increasing cognitive load designed to probe regions of the brain activated by attention and working memory. Resting-state fC measures spontaneous low frequency oscillations in MR signal in brain and is used to create maps of fC among brain regions. Results: There were no significant differences in n-back task performance between the CT group and controls. However, significant differences (p≤0.05) in task activation and fC between the two subjects groups were observed. N-back task activation was significantly greater in the BC group compared with controls in right inferior frontal gyrus and right cerebellum. There were significant interactions between subject group and cognitive load within right inferior parietal and left inferior occipital cortex. The default mode network consists of interconnected regions of the brain that are active while the subjects are at rest and reduce activity when subjects perform specific tasks. Within this network, the BC group has significantly less deactivation during task compared to controls. There were also differences between the groups in resting-state fC. Using the left amygdala as a seed region, changes in fC were seen in the pre-chemo scans of the BC group compared to the controls. The BC subjects showed a 185% increase in intraregional fC and increased fC with the superior temporal gyrus, an area along with the amygdala that is activated by emotional stimuli. These changes in fC may be due to increased stress response in BC subjects. After four sessions of CT the BC group showed significant decreases in fC between the amygdala and the parahippocampal gyrus, an area involved in encoding and retrieving memories. This decrease in functional connectivity along with alterations in brain activation by cognitive tasks may play a part in the memory and other cognitive complaints associated with cancer and CT and may inform the search for strategies to reduce CT associated cognitive dysfunction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2654. doi:1538-7445.AM2012-2654

Weight-Based Chemotherapy Dosing in Obese Patients With Cancer: Back to the Future

Weight-Based Chemotherapy Dosing in Obese Patients With Cancer: Back to the Future

Neuropsychological Performance in Survivors of Breast Cancer More Than 20 Years After Adjuvant Chemotherapy

Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment. This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis. The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance. Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting.

Randomized Trial Using Gonadotropin-Releasing Hormone Agonist Triptorelin for the Preservation of Ovarian Function During (Neo)Adjuvant Chemotherapy for Breast Cancer

Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.

P5-18-11: Incidence of Chemotherapy Dose Reductions and Dose Delays, and Reduced Chemotherapy Dose Intensity in Early Stage Breast Cancer.

Abstract Background: Chemotherapy is widely used to treat early stage breast cancer (ESBC). Dose reductions and dose delays–e.g., due to advanced age or severe/febrile neutropenia–are generally believed to increase risk of disease progression and reduce survival. Little is known about incidence of chemotherapy dose reductions and dose delays among women with ESBC in clinical practice. Methods: This study employed a retrospective cohort design and electronic medical records from over 60 community oncology clinics in more than 20 states (2004-2010). Study population included adult women who received myelosuppressive chemotherapy for ESBC (stages I-IIIA). For each such woman, each unique cycle of chemotherapy within their first observed course was identified. Incidences of chemotherapy dose delays (≥7 days for any drug in ≥1 cycles), chemotherapy dose reductions (≥15% for any drug in ≥1 cycles), and low relative chemotherapy dose intensity (&amp;lt;85% over the course) – relative to physician-reported planned chemotherapy administration – were descriptively analyzed for the seven most frequently observed regimens among subjects. Results: 2,350 women received seven most frequently observed regimens (80% of study population); mean age – across regimens – ranged from 51–56 years, and 31–94% received primary prophylaxis against severe/febrile neutropenia with a colony-stimulating factor. Incidence of dose reductions ranged from 17–48%, and dose delays, from 24–45%. Overall mean relative dose intensity (RDI) ranged from 80%-99%, and 17–50% of subjects received RDI &amp;lt;85%; mean RDI among those with low RDI ranged from 40%-67%. Discussion: Chemotherapy dose delays and dose reductions are common in ESBC, among those receiving dose-dense as well as conventional regimens. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-11.

Phase I/II Trial of Partial Breast Irradiation with Concurrent Dose-dense Doxorubicin and Cyclophosphamide (ddAC) Chemotherapy in Early-stage Breast Cancer: Late Assessment of Toxicity, Cosmetic Outcome, and Disease Recurrence

Phase I/II Trial of Partial Breast Irradiation with Concurrent Dose-dense Doxorubicin and Cyclophosphamide (ddAC) Chemotherapy in Early-stage Breast Cancer: Late Assessment of Toxicity, Cosmetic Outcome, and Disease Recurrence

121. Evaluating patterns of cytokine expression in women undergoing chemotherapy for early-stage breast cancer: A factor analytic approach

121. Evaluating patterns of cytokine expression in women undergoing chemotherapy for early-stage breast cancer: A factor analytic approach

FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer

BackgroundAntibody-dependent-mediated cytotoxicity (ADCC) is one of the modes of action for trastuzumab. Recent data have suggested that fragment C γ receptor (FcγR) polymorphisms have an effect on ADCC. This prospective phase II trial aimed to evaluate whether these polymorphisms are associated with clinical efficacies in patients who received trastuzumab. Patients and methodsPatients in a neoadjuvant (N) setting received Adriamycin and cyclophosphamide followed by weekly paclitaxel/trastuzumab. Patients in a metastatic (M) setting received single trastuzumab until progression. In total, 384 distinct single nucleotide polymorphisms of different FcγR, HER2, and fucosyltransferase loci were assessed. ResultsFifteen operable and 35 metastatic HER2-positive breast cancer patients were enrolled in each of the N and M settings, respectively. The FcγR2A-131 H/H genotype was significantly correlated with the pathologically documented response (pathological response) (P = 0.015) and the objective response (P = 0.043). The FcγR3A-158 V/V genotype was not correlated with the pathological response, but exhibited a tendency to be correlated with the objective response. Patients with the FcγR2A-131 H/H genotype had significantly longer progression-free survival in the M setting (P = 0.034). ConclusionThe FcγR2A-131 H/H polymorphism predicted the pathological response to trastuzumab-based neoadjuvant chemotherapy in early-stage breast cancer, and the objective response to trastuzumab in metastatic breast cancer.

Sleep Aid Prescribing Practices during Neoadjuvant or Adjuvant Chemotherapy for Breast Cancer

Sleep disruption is a common complaint in breast cancer patients receiving chemotherapy. We describe the sleep aid prescribing practices of oncologists treating women receiving adjuvant or neoadjuvant chemotherapy for breast cancer at a single institution. Subjects with early-stage breast cancer who received four cycles of neoadjuvant or adjuvant Adriamycin® and cyclophosphamide (AC) at the University of California, San Diego over a 2-year period were evaluated by retrospective chart review. Clinical data pertinent to sleep disorders and electronic prescriptions for sleep aids were collected using the electronic medical record. Of the 124 breast cancer subjects, 52.4% discussed sleep with their provider. Whereas 13.7% of subjects reported prior sleep aid use, 32.3% were prescribed sleep aids during chemotherapy, most commonly lorazepam (31.4%) and zolpidem (29.4%). Women prescribed sleep aids during chemotherapy were significantly more likely to discuss sleep with their provider, more likely to have been taking sleep aids previously, and more likely to be taking psychiatric medications. Sleep disturbances during AC chemotherapy for early-stage breast cancer are common and are frequently treated with sleep aid medications. We show that women with prior sleep aid use and concurrent psychiatric medication use were more likely to need sleep aids during chemotherapy, suggesting these are high-risk populations that could be targeted for intervention prospectively.

Can some patients avoid adjuvant chemotherapy for early-stage breast cancer?

Adjuvant chemotherapy reduces the risk of relapse and mortality for women with early-stage breast cancer. However, many women diagnosed with early-stage breast cancer experience the toxic effects associated with adjuvant chemotherapy without any meaningful benefit. There are a variety of clinicopathological factors--including hormone receptor expression, histology, and proliferation markers such as Ki-67--that can be used to try to identify patients who can safely avoid adjuvant chemotherapy. In addition, novel molecular tools, including the intrinsic molecular subtypes, prognostic multigene assays, and levels of urokinase-type plasminogen activator, provide further prognostic and predictive information to the standard clinicopathological factors thereby improving the accuracy of risk-of-relapse estimation and of the likelihood of response to cytotoxic chemotherapy.