Moderate neutropenia with adjuvant CMF confers improved survival in early breast cancer.
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ABSTRACT:
SUBMITTER: Cameron DA
PROVIDER: S-EPMC2394463 | biostudies-other | 2003 Nov
REPOSITORIES: biostudies-other
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Project description:Most chemotherapy regimens cause neutropenic nadirs between days 10 and 14, and administration of granulocyte colony-stimulating factor (G-CSF) support relies on this timing. In docetaxel (DOC)-based chemotherapy, the frequency of febrile neutropenia (FN) and the G-CSF dose administered varied greatly between studies. Our study goal was to forecast the necessary dose of G-CSF by comparing day 8 neutropenia with putative changes within the neutrophil pool. We conducted a retrospective observational analysis of 242 early breast cancer patients who had received adjuvant DOC-based chemotherapy (DOC group) compared with 43 patients who had received FEC chemotherapy (FEC group). Patients who were given a standard dose and had a blood test on day 8 in the 1st cycle were eligible. In the DOC group, patients routinely received prophylactic administration of G-CSF (150 μg/body) on day 3 and received additional G-CSF based on a blood test on day 8. Results of the day 8 blood test showed that severe neutropenia (<500/mm3, average 494/mm3) was observed in 152 out of 242 (62.8%) patients in the DOC group, while in the FEC group (n = 43), neutropenia was ambiguous (average 1,741/mm3). In the FEC group, 9 out of 43 patients (20.9%) and in the DOC group, 27 out of 242 patients (11.1%) experienced FN. In the DOC group, day 8 neutropenia was predictive for FN in a logistic regression model (OR 0.79 [95% CI: 0.655-0.952], p = 0.013). Among 214 patients under 70 years old, the planned chemotherapy cycle was completed in 190 (88.8%) patients who also received the maximum dose of G-CSF (150 μg/body) four times, while 23 patients could not complete the planned chemotherapy cycle, but only five because of FN-related complications. Patients treated with DOC should be treated for primary prophylaxis with G-CSF support at an earlier time starting with a relatively small dose.
| S-EPMC6472781 | biostudies-literature
Project description:Known gene mutations account for approximately 50% of the hereditary risk for breast cancer. Moderate and low penetrance variants, discovered by genomic approaches, account for an as-yet-unknown proportion of the remaining heritability. A truncating mutation c.325C>T:p.Arg109* (R109X) in the ATP-dependent helicase ERCC3 was observed recurrently among exomes sequenced in BRCA wild-type, breast cancer-affected individuals of Ashkenazi Jewish ancestry. Modeling of the mutation in ERCC3-deficient or CRISPR/Cas9-edited cell lines showed a consistent pattern of reduced expression of the protein and concomitant hypomorphic functionality when challenged with UVC exposure or treatment with the DNA alkylating agent IlludinS. Overexpressing the mutant protein in ERCC3-deficient cells only partially rescued their DNA repair-deficient phenotype. Comparison of frequency of this recurrent mutation in over 6,500 chromosomes of breast cancer cases and 6,800 Ashkenazi controls showed significant association with breast cancer risk (ORBC = 1.53, ORER+ = 1.73), particularly for the estrogen receptor-positive subset (P < 0.007).SignificanceA functionally significant recurrent ERCC3 mutation increased the risk for breast cancer in a genetic isolate. Mutated cell lines showed lower survival after in vitro exposure to DNA-damaging agents. Thus, similar to tumors arising in the background of homologous repair defects, mutations in nucleotide excision repair genes such as ERCC3 could constitute potential therapeutic targets in a subset of hereditary breast cancers. Cancer Discov; 6(11); 1267-75. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1197.
| S-EPMC5614601 | biostudies-literature
Project description:The UK audit was undertaken in primary breast cancer patients receiving adjuvant chemotherapy to: (1) record the incidence of neutropenic events (hospitalisation due to febrile neutropenia, dose delay of > or =1 week or dose reduction of > or =15% due to neutropenia); (2) evaluate the impact of neutropenic events on overall dose intensity (DI) received and (3) review the use of granulocyte colony-stimulating factor (G-CSF) in clinical practice. Data from 422 patients with Stage I-III breast cancer were collected from 15 centres. Cyclophosphamide, methotrexate and 5-fluorouracil(CMF)- or anthracycline-based regimens were the most commonly used. Only 5.2% of patients received G-CSF. Overall, 29% of patients experienced a neutropenic event, most frequently dose delay. Neutropenic events had a significant impact on the ability to deliver planned DI. Out of 422 patients, 17% did not achieve 85% of their planned DI; due to neutropenia in 11% of patients. Of the neutropenic patients receiving CMF- or anthracycline-based regimens, around 40 and 32% of patients, respectively, did not achieve 85% of their planned DI. Patients who experienced one neutropenic event had a higher risk of a second event. During adjuvant chemotherapy of primary breast cancer, neutropenic events are common, likely to occur in subsequent chemotherapy cycles, and have a significant impact on receiving planned DI.
| S-EPMC2376842 | biostudies-other
Project description:Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.
| S-EPMC4197909 | biostudies-other
Project description: Not available
| S-EPMC6718224 | biostudies-literature
Project description:BackgroundBreast conserving surgery (BCS) and adjuvant hormonal therapy (HT) without radiation therapy (RT) is an acceptable approach for older women with early stage, estrogen receptor (ER) positive breast cancer. Toxicity and compliance remain issues with HT. Adjuvant RT alone may have better compliance, but its efficacy in the absence of HT is unclear. We aim to assess patterns of adjuvant therapy and survival outcomes among older women with early stage, ER positive (ER+) breast cancer.MethodsThe National Cancer Data Base (NCDB) was used to identify 130,194 women age ≥65 years with invasive ER+, node negative breast cancer diagnosed between 2004 and 2015. All patients underwent BCS. Kaplan-Meier survival curves were used to examine overall survival (OS). The association between adjuvant therapy and OS was assessed in multivariable Cox proportional hazards regression models.ResultsUnadjusted 5/10-year OS rates were 90.0%/64.3% for HT and RT, 84.2%/54.9% for RT alone, 78.7%/44.5% for HT alone, and 71.6%/38.0% for no treatment; p<0.001 for all. Compared to HT alone, the 10-year multivariable hazard ratio (HR) for death for RT alone was 0.86 (95% CI 0.82-0.91). In propensity-matched patients who received RT alone or HT alone (n=21,326), RT alone had significantly better survival at 5 (HRadj : 0.84) and 10 (HRadj : 0.87) years.ConclusionsOlder women with early stage ER+ breast cancer who undergo BCS and receive both HT and RT have the best survival, while RT as single-modality therapy had higher rates of OS at 5 and 10 years compared to HT alone.
| S-EPMC7666745 | biostudies-literature
Project description:Background:In premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown. Methods:In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor-positive and -negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided. Results:A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor-positive disease. Median age was 43 (interquartile range = 38-47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab?lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (Pinteraction for DFS = .007; Pinteraction for OS = .003). For hormone receptor-positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor-negative patients. Conclusions:In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor-positive/HER2-positive early breast cancer patients.
| S-EPMC6335113 | biostudies-literature
Project description:BackgroundGermline BRCA1/2 pathogenic variant (PV) carriers have high lifetime risk of developing breast cancer and therefore subjected to intense lifetime screening. However, solid data on the effectiveness of high-risk screening of the BRCA1/2 carrier population is limited.Patients and methodsRetrospectively, we analyzed 346 women diagnosed with breast tumors. Patients were divided according to the timing of BRCA1/2 PVrecognition, before (BRCA-preDx awareness, N = 62) or after (BRCA-postDx awareness group, N = 284) cancer diagnosis.ResultsMedian follow-up times were 131.42 and 93.77 months in the BRCA-preDx awareness and BRCA-postDx awareness groups, respectively. In the BRCA-preDx awareness group, 78.7% of the patients had invasive tumors and 21.3% were diagnosed with pure ductal carcinoma in situ. In contrast, in the BRCA-postDx awareness group over 93% of women were diagnosed with invasive cancer and only 6.4% had in situ disease. The mode of tumor detection differed significantly between the groups: 71.9% in the BRCA-postDx awareness group and 26.2% in the BRCA-preDx awareness group were diagnosed after personally palpating a lump. Tumor size and nodal involvement were significantly more favorable in the BRCA-preDx awareness group. T stage was significantly lower in the BRCA-preDx awareness group: 54.84% at T1 and 20.96% at Tis. In the BRCA-postDx awareness group, only 37.54% were at T1 and 6.49% at Tis. The N stage was also significantly lower in the BRCA-preDx awareness group: 71% had no lymph node metastases, compared with 56.1% in the BRCA-postDx awareness group. Additionally, therapeutic procedures varied between the groups: BRCA-preDx awareness group patients underwent more breast conserving surgeries. Axillary lymph node dissection was done in 38% of women in the BRCA-postDx awareness group and in only 8.7% of the BRCA-preDx awareness group patients. Interestingly, improved survival was found among patients who underwent high-risk screening (hazard ratio=0.34).ConclusionsHigh-risk screening might facilitate downstaging of detected breast tumor among BRCA1/2 carrier population.
| S-EPMC8443779 | biostudies-literature
Project description:BACKGROUND: We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. METHODS: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. RESULTS: The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. CONCLUSIONS: The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.
| S-EPMC4150261 | biostudies-other
Project description:Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.
| S-EPMC4224200 | biostudies-literature