Background
Febrile neutropenia (FN) is one of the most common and most critical adverse effects of chemotherapy. Despite many existing guidelines based on the use of granulocyte-colony stimulating ...factor (G-CSF), FN continues to impair the quality of life and interfere with the treatment of many patients. The purpose of this study was to assess the incidence and management of FN associated with chemotherapy for early breast cancer in routine clinical practice.
Methods
All patients with early-stage breast cancer (ESBC) treated by chemotherapy at Institut Curie, Hôpital René Huguenin, in 2014 were retrospectively included. The incidence and management of FN were reported. Risk factors associated with FN were studied by robust-error-variance Poisson regression.
Results
A total of 524 patients received either neoadjuvant (
N
= 130) or adjuvant chemotherapy (
N
= 394). Most patients (80%) were treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC100; 3 cycles) followed by docetaxel 100 mg/m
2
(D; 3 cycles). The overall incidence of FN was 17%. Eighteen percent of patients received primary prophylaxis (PP) for FN with G-CSF, using pegfilgrastim in 64% of cases and 74% of patients over the age of 70 received PP. Less than 5% of patients who received PP experienced FN. Recurrent FN after secondary prophylaxis was observed in 9% of patients. Forty-seven percent of cases of FN occurred after the first cycle and 30% occurred after the fourth cycle, corresponding to D ± trastuzumab (T). The FEC100 regimen was associated with a relative risk of FN of 1.98 (
p
= 0.09). Autoimmune (AI) and inflammatory diseases were associated with a higher risk of FN (RR 3.08;
p
< 0.01). No significant difference in the incidence of FN was observed between adjuvant and neoadjuvant chemotherapy. FN was managed on an outpatient basis in 72% of cases. Outpatients with FN were mainly treated by a combination of amoxicillin–clavulanic acid and ciprofloxacin. Dose reduction or chemotherapy regimen modification were necessary in 25% of patients after FN. No toxic death was reported.
Conclusion
The incidence of FN induced by adjuvant/neoadjuvant chemotherapy in ESBC is higher in routine clinical practice than in clinical trials. AI or inflammatory diseases were significant independent risk factors for FN. Primary prophylaxis in patients at risk (elderly, comorbid patients), especially treated with the FEC regimen, is the keystone of management of this adverse effect. Prevention and management of FN to ensure the patient’s safety and quality of life are a major issue for both medical oncologists and supportive care physicians.
The actual improvement of epidemiologic database collection concerning bone metastases of solid tumors allows us to better understand the seriousness of this evolution, its human, social and ...financial burden. A renewal of interest appeared with a better screening of the asymptomatic forms and by the therapeutic advances obtained by bone resorption inhibitors. They were developed in clinical trials with a specific and original methodology evaluating their efficacy on the skeletal-related events (SRE) (pain, fracture, spinal cord compression, pathologic fracture and hypercalcemia). It is a major concern for the clinician, whatever his specialization (medical oncology, radiotherapist, surgeon, supportive care expert), to recognize these SRE for an early diagnosis and treatment since they are, with the primary tumor, the most important prognostic factors for patient's survival.
To develop a specific prognostic score for patients with brain metastases (BM) from breast cancer (BC), including the BC molecular subtype and treatment parameters, we analyzed the outcome of 130 ...patients with BM from BC who received whole-brain radiotherapy. We identified hierarchical risk groups for estimated survival by using recursive partitioning analysis (RPA). Seven prognostic factors, namely performance status, age, trastuzumab-based therapy for HER-2-overexpressing tumors, a triple-negative phenotype, Scarff-Bloom-Richardson grade, the serum LDH level and the lymphocyte count at BM diagnosis, were incorporated in the RPA. The final RPA nodes were grouped according to the survival time. The RPA tree showed that survival was best (median 19.5 months) among patients with HER2-overexpressing tumors who received trastuzumab-based therapy. The worst survival (median 3.5 months) was observed among patients who did not receive trastuzumab and who had lymphopenia at BM diagnosis, or KPS <70 and age over 50 years, or KPS ≥70 and a triple-negative tumor (HR− & HER-2−). The other patients had a median survival of 12.5 months (
P
< 0.001). This 3-class specific prognostic score successfully predicted the outcomes of a heterogeneous group of patients with brain metastases from BC.
Previous qualitative and intentions surveys have shown that the disclosure of a
BRCA1
/
2
mutation might deter young women from becoming pregnant. However, to our knowledge, no comparative studies ...have ever documented the possibility that positive genetic test results might affect these women’s future reproductive rates. Our aim was therefore to quantify the impact of
BRCA1
/
2
mutation disclosure on long-term relationships between partners and childbearing rates. Participants were cancer-free women belonging to families in which a deleterious
BRCA1
/
2
mutation had been identified, who had attended one of the 29 participating cancer genetic clinics for
BRCA1
/
2
testing between 2000 and 2006. Logistic regression models were used to determine predictors of the 5-year self-reported parenthood rate. The sample consisted of 271 women aged 18–45 years (126
BRCA1
/
2
mutation carriers and 145 non-carriers). Couples had separated more frequently among
BRCA1
/
2
carriers than non-carriers (10 vs. 3 %,
p
= .040), especially among nulliparous carriers (13 %). Among the 104 women who were childless at disclosure, disclosure of a
BRCA1
/
2
mutation was not significantly associated with childbearing during the 5-year follow-up period adjusted odds ratio .64, 95 % confidence interval (CI) (.26, 1.57),
p
= .334. Among the 167 women with at least one child at disclosure of a
BRCA1
/
2
mutation had no conspicuous effect on the childbearing trends adjOR .88, 95 % CI (.35, 2.21),
p
= .787. The disclosure of a
BRCA1
/
2
mutation might impact couples’ relationships and future mothering rates, particularly among nulliparous women. Studies on larger populations are now required to confirm these findings.
Abstract Rationale Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the ...need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients’ autonomy. Design and methods In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or “high risk” pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete. Results Forty patients (median age 75 70–82) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred. Conclusion This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment.
Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes, and the effect of reproductive ...factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.
We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.
We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.
As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones.
Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers.
This study aimed to measure patients' smoking patterns for 5 years after BRCA1/2 test result disclosure.
A national cohort consisting of 621 French cancer-free women from families with BRCA1/2 ...mutations (mean age (SD): 40.5 years (11.5 years)) were included from December 1999 to January 2006, before disclosure of genetic test results, and followed for 5 years. They completed self-administered questionnaires about their cigarette smoking behaviors before receiving their test results (baseline) and 6, 12, 24, and 60 months after disclosure. Multivariate statistical analyses of the changes in participants' smoking behaviors were performed using a zero-inflated Poisson mixed model.
Baseline smoking was found to depend on age, educational level, marital status, alcohol consumption, body mass index, and cancer risk perception. The zero-inflated part of the model showed the occurrence of no significant changes in the percentage of smokers during the 5 years after disclosure of the BRCA1/2 test results; however, daily smoking among BRCA1/2 carriers decreased significantly compared with that of noncarriers (adjusted hazard ratio = 0.83; (95% confidence interval: 0.69-0.99); P = 0.04) after adjusting for baseline smoking behavior.
It would be worth investigating the possibility of counseling women during the genetic testing process about the multiple risk factors involved in cancer, such as genetic and lifestyle factors.
PDF
