The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age

BackgroundThe majority of breast cancer patients are postmenopausal women who are increasingly being offered adjuvant chemotherapy. Since the beneficial effect of chemotherapy in postmenopausal patients predominantly occurs in the first 5 years after diagnosis, a prognostic marker for early events can be of use for adjuvant treatment decision making. The aim of this study was to evaluate the prognostic value of the 70-gene prognosis signature for early events in postmenopausal patients.MethodsFrozen tumor samples from 148 patients aged 55–70 years were selected (T1–2, N0) and classified by the 70-gene prognosis signature (MammaPrint™) into good or poor prognosis. Eighteen percent received hormonal therapy.ResultsBreast cancer-specific survival (BCSS) at 5 years was 99% for the good-prognosis signature versus 80% for the poor-prognosis signature group (P = 0.036). The 70-gene prognosis signature was a significant and independent predictor of BCCS during the first 5 years of follow-up with an adjusted hazard ratio of 14.4 (95% confidence interval 1.7–122.2; P = 0.01) at 5 years.ConclusionThe 70-gene prognosis signature can accurately select postmenopausal patients at low risk of breast cancer-related death within 5 years of diagnosis and can be of clinical use in selecting postmenopausal women for adjuvant chemotherapy.     

Age-related differences in persistence in women with breast cancer treated with tamoxifen or aromatase inhibitors in Germany

AimsTo study age-related persistence in postmenopausal women with endocrine-responsive breast cancer treated with tamoxifen (TAM) and aromatase inhibitors (AI).MethodsData on 29,245 patients diagnosed with metastatic or non-metastatic breast cancer (BC) and initially treated with TAM or AI between 2004 and 2013 were included. The primary outcome measure was the age-dependent rate of discontinuation of endocrine treatment within 5 years after initiation. Discontinuation of therapy was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance type (private/statutory), type of care (gynecological/general), region (West/East Germany), concomitant diagnoses (depression, osteoporosis, and diabetes), and Charlson Comorbidity Score were included as covariates.ResultsThe mean ages of the women in the < 70 and ≥ 70 groups were 55.9 (SD: 9.7) and 77.4 (SD: 5.4) years, respectively. Within 5 years after treatment initiation, 88.8% of women < 70 of age and 82% of women ≥ 70 years of age had terminated treatment (p-value < 0.001). Patients aged ≥ 70 exhibited a lower risk of treatment discontinuation than patients aged < 70 (HR = 0.75, 95% CI: 0.66–0.85). Furthermore, gynecological practices, disease management programs, and high Charlson scores increased persistence.ConclusionsOverall, the present study indicates that persistence rates are low in both women with BC aged < 70 and those aged ≥ 70 years. We also found that younger women with BC are at a higher risk of treatment discontinuation than older women.     

Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (≥ 70 years)

BackgroundWe conducted a multicenter prospective trial to assess tolerability and activity of pegylated liposomal doxorubicin (PLD) in women ≥ 70 years with locally-advanced or metastatic breast cancer.Patients and MethodsAll patients underwent Multidimensional Geriatric Assessment (MGA). Frail patients were excluded. Normal cardiac function was required for inclusion. A bi-weekly schedule of PLD at 20 mg/mq was adopted.ResultsThirty-two patients were enrolled with a median age of 78 years, 78.1% with visceral involvement, and 37.6% previously treated with chemotherapy for advanced disease. A mean of 7.8 cycles were delivered (range 1 to 20), with a median cumulative dose intensity of 8.9 mg/m²/week. Grade 3–4 toxicities were anemia (6.3%), palmar–plantar erythrodysesthesia (6.3%), mucositis (6.3%), infection (3.1%), and pulmonary embolism (3.1%). No cardiac events were registered. Causes of treatment interruption were maximal response (15.6%), progression (40.6%), refusal/loss to follow-up (28.1%), toxicities (9.4%), or other (6.3%). Response was obtained in 33.3% of 27 evaluable patients; median time to progression (TTP) was 10.3 months. MGA status (vulnerable vs. fit) did not have an impact on response, progression, and toxicity.ConclusionsBi-weekly PLD is well tolerated in both fit and vulnerable patients, with an apparently fairly good response rate and TTP (possibly biased by subsequent endocrine therapy and loss to follow-up). Close observation of patients is recommended in order to avoid early refusal/loss to follow-up.     

Adjuvant chemotherapy and differential invasive breast cancer specific survival in elderly women

ObjectiveTo assess adjuvant chemotherapy recommendations, administration and disease-specific survival for invasive breast cancer (BC) among patients 75 years and older compared with that of younger women.Materials and MethodsA cohort of patients with primary breast cancer, aged 65–94, stages I–III from 1990 to 2010 was identified and tracked by our breast cancer registry (n = 2329). Stage, treatment recommendations and outcomes were chart abstracted at diagnosis and follow-up. Associations were tested with logistic regression and the Kaplan–Meier method was used for disease-specific survival (DSS).ResultsSeventy-five percent of patients aged 75 + were seen by an oncologist compared with 78% aged 70–74 and 84% aged 65–69. Women aged 75 + seen by an oncologist were more likely age 75–79, stage II/III, hormone receptor negative (HR ?) or her-2/neu positive. Of these patients, age, stage and HR status were related to a chemotherapy recommendation. Of 106 patients recommended for chemotherapy, 18 refused (17%) and 24 did not complete treatment due to complications, patient choice, disease progression or death not related to treatment. DSS was equivalent for patients 75 and older with stage I BC compared to 65–74 year olds, but significantly worse in stage II and III patients, respectively (stage II 5 year DSS 90% vs. 97%, stage III 5 year DSS 65% vs. 81%).ConclusionPatients aged 75 and older with invasive breast cancer who were recommended for adjuvant chemotherapy have a high rate of refusal and complications from therapy. Their disease specific mortality disadvantage is restricted to stage II and III patients, a group in need of effective therapy to improve disease survival.     

Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy

BackgroundEpirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect.MethodsWe re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin–cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m²) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m²)]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF) < 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II–IV).Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables.ResultsAmong the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15–24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels.ConclusionsParticipation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.     

Has breast cancer in the elderly remained the same over recent decades? A comparison of two groups of patients 70 years or older treated for breast cancer twenty years apart

ObjectivesBreast cancer (BC) in the elderly population is by far the most frequent malignancy in Western countries; however, little evidence is available regarding the specific management of this group. The purpose of this study was to identify how the biological and clinical characteristics of cancer have changed over the past 20 years by comparing two groups of elderly patients with breast cancer operated on 20 years apart. The secondary endpoint was to underline potential changes in surgical strategy over the past 20 years.Materials and MethodsOne group of consecutive elderly patients undergoing surgery for BC between January 1990 and December 1993 (Group A), and one group undergoing surgery between January 2008 and December 2011 (Group B) were identified and analyzed. Data regarding surgical treatment, stage, tumor grading, hormonal and HER2/neu receptors, and Ki-67 were collected and compared.ResultsA total of 422 elderly patients underwent surgical treatment, 142 in Group A and 280 in Group B. An earlier stage at presentation was detected in Group B, T1 (57.5% B vs. 31.6% A) and N0 (64.6% B vs. 54.2% A). Surgical treatment in the first group was more extensive while conservative procedures were more frequently performed in the second group. Despite the earlier presentation, tumor grade was higher in Group B (G3 10.6% A vs. 32.1% B, p < 0.05). Overexpression of Ki-67 was again more frequent in Group B (56.2% B vs. 32.5% A, p < 0.05). Hormonal and HER2/neu receptor expression was comparable.ConclusionsNowadays, elderly patients with BC are more likely to present at an early stage; therefore, conservative surgery is a feasible option. Despite potential bias related to changes of pathology and immunohistochemistry examination techniques over the decades, the biological characteristics of recent patients with BC seem to be consistent with more aggressive tumors. Tailored treatment should be offered with regard to biological age, the cancer-specific profile and active life expectancy.     

Local recurrence following breast-conserving treatment in women aged 40 years or younger: Trends in risk and the impact on prognosis in a population-based cohort of 1143 patients

AimTo evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a large, population-based cohort of women aged ?40 years with early-stage breast cancer.MethodsAll women (n = 1143) aged ?40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast.ResultsAfter a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively (p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (?5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407).ConclusionLocal control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.     

Treatment-related differences in health related quality of life and disease specific symptoms among colon cancer survivors: Results from the population-based PROFILES registry

BackgroundThe goal of this study was to compare health related quality of life (HRQoL) and disease-specific symptoms between colon cancer patients treated with surgery only (SU) and surgery and adjuvant chemotherapy (SU + adjCT). Results were stratified for those aged <70 and ⩾70 years. HRQoL of patients was also compared with an age- and sex-matched normative population.MethodsPatients diagnosed with colon cancer between January 2000 and June 2009, as registered within the population-based Eindhoven Cancer Registry, received a questionnaire on HRQoL (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire version 3.0 (QLQ-C30)) and disease-specific symptoms (EORTC QLQ-Colorectal 38 (EORTC QLQ-CR38)) in 2010. The first was also completed by the normative population (n = 685).Results1606 (72%) colon cancer survivors responded to our questionnaire. 1542 colon cancer patients treated with SU (n = 1031) or SU + adjCT (n = 493) were included in this study. In colon cancer patients aged <70 years and aged ⩾70 no statistical significant differences on the subscales of the EORTC QLQ-C30 or the EORTC QLQ-CR38 were observed between patients treated with SU and SU + adjCT. Colon cancer patients aged <70 years either treated with SU or SU + adjCT reported significantly more insomnia, diarrhoea and financial problems compared with the normative population. No differences in HRQoL were found between colon cancer patients aged ⩾70 years either treated with SU or SU + adjCT and the normative population.ConclusionNo differences in HRQoL and disease-specific symptoms were found between patients treated with SU versus SU + adjCT in both younger and elderly colon cancer patients. Withholding patients adjCT, based on concerns for long-term HRQoL or disease-specific symptoms does therefore not seem plausible.     

Health-related quality of life 14 years after preoperative short-term radiotherapy and total mesorectal excision for rectal cancer: Report of a multicenter randomised trial

BackgroundPreoperative short-term radiotherapy (PRT) in combination with total mesorectal excision (TME) has shown to improve local control in rectal cancer treatment, however without a survival benefit and at the cost of increased morbidity. The current study investigates the long-term health-related quality of life (HRQL) of patients 14 years after treatment in the Dutch TME trial.MethodsIn the TME trial (1996–1999) 1530 Dutch patients with rectal cancer were treated with TME and randomly assigned to PRT (5 × 5 Gy). In 2012 HRQL was evaluated in surviving patients (n = 606) using a questionnaire combining EORTC QLQ-C30, EORTC QLQ-CR29 and additional questions.FindingsResults were obtained from 478 patients (82%), with a median follow up of 14 years. PRT + TME patients without stoma reported more faecal leakage and higher stool frequency, resulting in increased need of pads. Furthermore, irradiated males reported more erection problems. However, radiotherapy did not have negative effects on overall functioning. Compared with Dutch population, patients in both treatment arms reported a small decrease in overall functioning and males reported less sexual activity, interest and enjoyment and more erection difficulties. Irradiated females reported more vaginal dryness and more pain at intercourse compared with Dutch population.InterpretationLong-term HRQL evaluation shows that treatment-related symptoms are still present 14 years after treatment for rectal cancer. Radiotherapy increased bowel dysfunction in patients without stoma. Compared with the Dutch population, both groups reported increased sexual dysfunction. Despite these treatment-related symptoms, there was no difference in overall functioning and global health between TME and PRT + TME.     

Management of breast cancer after Hodgkin’s lymphoma and paediatric cancer

RationaleThe risk of women developing a breast cancer (BC) after receiving chest radiotherapy for paediatric cancers and Hodgkin lymphomas is well established. The aim of this study was to assess these patients’ clinical characteristics and clinical outcomes.MethodsThe study concerns women with a history of primary neoplasms treated with chest irradiation ± chemotherapy and subsequently diagnosed with BC.ResultsWe identified 78 women who developed BC (invasive in 68 cases, 87%). They were a median 18 and 38 years of age when their first neoplasm and BC were diagnosed, respectively. Breast-conserving surgery was performed in 39 patients, and 32 underwent breast irradiation. Twenty of the 41 patients (49%) treated with chemotherapy received an anthracycline-containing regimen.The 5- and 11-year event free survival (EFS) and overall survival (OS) rates were 69% and 42%, respectively. Nine patients (12%) developed a third cancer and 18 (23%) a cardiovascular event. Of the 68 women with invasive BC, the first event involved contralateral BC in 55% of cases: time to progression (TTP) rates were 70% and 47% at 5 and 11 years. The 5- and 11-year BC-specific survival rates (BCSS) were 84% and 68%, respectively.ConclusionsJudging from our experience, survival rates after BC developing in women previously given chest radiotherapy are not dissimilar to those observed in other women with primary BC. Given the far from negligible risk of subsequent cancers and cardiovascular events, it is mandatory to discuss the best choice of treatment for such patients in terms of their chances of cure and quality of life, and also the risks of late sequelae.     

Treatment of breast cancer in the elderly: A prospective,population-based Swiss study

ObjectivesThe primary objective of this population-based study is to describe the patterns of care of elderly patients with breast cancer (BC), and evaluate potential causative factors for the decrease in BC-specific survival (BCSS) in the elderly.Patients and MethodsWe included all or representative samples of patients with newly diagnosed BC from seven Swiss cancer registries between 2003 and 2005 (n = 4820). Surgical and non-surgical BC treatment was analyzed over 5 age groups (< 65, 65 to < 70, 70 to < 75, 75 to < 80 and ≥ 80 years), and the predictive impact of patient age on specific treatments was calculated using multivariate logistic regression analysis.ResultsThe proportion of locally advanced, metastatic and incompletely staged BC increased with age. The odds ratio for performing breast-conserving surgery (BCS) in stages I–II BC (0.37), sentinel lymph node dissection (SLND) in patients with no palpable adenopathy (0.58), post-BCS radiotherapy (0.04) and adjuvant endocrine treatment (0.23) were all in disfavor of patients ≥ 80 years of age compared to their younger peers. Only 36% of patients ≥ 80 years of age with no palpable adenopathy underwent SLND. In the adjusted model, higher age was a significant risk factor for omitting post-BCS radiotherapy, SLND and adjuvant endocrine treatment.ConclusionsThis study found an increase in incomplete diagnostic assessment, and a substantial underuse of BCS, post-BCS radiotherapy, SLND and adjuvant endocrine treatment in elderly patients with BC. There is a need for improved management of early BC in the elderly even in a system with universal access to health care services.     

An evaluation of elderly patients (≥ 70 years old) enrolled in Phase I clinical trials at University of Texas Health Science Center at San Antonio-Cancer Therapy Research Center from 2009 to 2011

ObjectiveElderly patients with cancer are under-represented in clinical trials, and there is especially scant data on their participation in early-phase trials. In an effort to provide more data, we reviewed our Phase I experience.MethodsWe conducted a retrospective analysis of 461 patients enrolled in Phase I clinical trials at the Cancer Therapy Research Center (CTRC) from 2009 to 2011 to determine the rate of completion of at least 12 weeks of treatment, incidence of adverse events, prevalence of co-morbidities, functional status, and survival. Elderly (E) was defined as ≥ 70 years; non-elderly (NE) was defined as ≤ 69 years.ResultsThe elderly represented 15% (69/461) of enrolled patients. The most common malignancies were colon (20%), hematologic (18%), lung (15%), and breast (8%). The median age of E was 72 years (range 70–85, SD 3.15), and 49% of the E was female. Co-morbidities (E vs. NE) include diabetes (28% vs. 23%), hypertension (65% vs. 44%), and chronic kidney disease (91% vs. 48%). Thirty-two percent of E vs. 37% of NE completed at least 12 weeks of treatment. Reasons for not completing in E vs. NE respectively were progression of disease (43% vs. 61%), toxicity (28% vs. 9%), and self-withdrawal (11% vs. 7%). Reasons for not completing the protocol was significantly associated with being elderly (p = 0.005). There were non-significant differences in toxicity in E vs. NE.ConclusionElderly patients have a higher likelihood of not completing trials for reasons including toxicity. This highlights the need for better Phase I trial-designs incorporating ideal geriatric assessment tools.     

Feasibility of radiation therapy in patients 90 years of age and older: A French multicentre analysis

BackgroundThere are only scarce data on the management of patients aged 90 years or older with cancer, and more particularly on the place of radiation therapy (RT). We report the first large study on patients (pts) aged 90 years or older receiving RT.Methods and materialsRecords from RT departments from five institutions were reviewed to identify pts 90 years of age and older who underwent RT for various malignant tumours treated between 2003 and 2012. Tumours’ characteristics were examined, as well as treatment specificities and treatment intent.Results308 pts receiving 318 RT courses were identified, mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 44% and 56%, respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery and tumour stage. Median total prescribed dose was 36 Gy (4–76 Gy). Hypofractionation and split course were used in 88% and 7.3%, respectively. Most toxicities were mild to moderate. RT could not be completed in 23 pts (7.5%). No long-term toxicity was reported. Median overall survival was 22.9 months (95CI: 15.5–42.7 months). Cancer was the cause of death in 8.7% and 46% of pts treated with curative and palliative intent, respectively.ConclusionThis study shows that RT is feasible for patients aged 90 years or more. PS, place of life and tumour stage were factors of the therapeutic decision. There is no reason to withdraw pts with good general health condition from potentially curative RT, provided that careful attention is paid to factors of toxicity and to geriatric vulnerabilities.     

Common breast cancer risk alleles and risk assessment: a study on 35 441 individuals from the Danish general population

BackgroundWe hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography.Participants and methodsAbout 35 441 individuals from the Danish general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0–2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer.ResultsBreast cancer incidence in the 19 010 women was increased across allele sum quintiles (log-rank trend test; P = 1×10 ^− 12), but not incidence of other cancers (P = 0.41). Age- and study-adjusted hazard ratio for the fifth versus the first allele sum quintile was 1.82 (95% confidence interval; 1.53–2.18). Corresponding hazard ratios per allele were 1.04 (1.03–1.05) and 1.05 (1.02–1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year-old women, the starting age for screening mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the first through fifth quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50–69 years, and 94% of women aged 40–49 years, had absolute 5-year breast cancer risks ≤ 1.5%. Using polygenic risk score led to similar results.ConclusionCommon breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50-year-old woman.     

Long-term outcomes among African–American and white women with breast cancer: What is the impact of comorbidity?

ObjectivesWe examined the association between comorbidity and long-term mortality from breast cancer and other causes among African–American and white women with breast cancer.MethodsA total of 170 African–American and 829 white women aged 40–84 years were followed for up to 28 years with median follow-up of 11.3 years in the Health and Functioning in Women (HFW) study. The impact of the Charlson Comorbidity Score (CCS) in the first few months following breast cancer diagnosis on the risk of mortality from breast cancer and other causes was examined using extended Cox models.ResultsMedian follow-up was significantly shorter for African–American women than their white counterparts (median 8.5 years vs. 12.3 years). Compared to white women, African–American women had significantly fewer years of education, greater body mass index, were more likely to have functional limitations and later stage at breast cancer diagnosis, and fewer had adequate financial resources (all P < 0.05). Proportionately more African–American women died of breast cancer than white women (37.1% vs. 31.4%, P = 0.15). A positive and statistically significant time-varying effect of the Charlson Comorbidity Score (CCS) on other-cause mortality persisted throughout the first 5 years of follow-up (P < 0.001) but not for its remainder.ConclusionsHigher CCS was associated with increased risk of other-cause mortality, but not breast cancer specific mortality; the association did not differ among African–American and white women.     

Utility of the CPS + EG staging system in hormone receptor-positive,human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy

BackgroundPathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS + EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) patients and compares the results to a cohort of unselected patients.MethodsThe CPS + EG score was calculated for 6637 unselected patients and 2454 patients with HR + /HER2− tumours who received anthracycline/taxane-based NACT within 8 prospective German trials.ResultsFive-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR + /HER2− subgroup, respectively. The CPS + EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS + EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS + EG score to the HR + /HER2− subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population.ConclusionsIn HR + /HER2− patients, the CPS + EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer.     

Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence: A population-based cohort study

IntroductionWhen risk estimation in older patients with hormone receptor positive breast cancer (HR + BC) is based on the same factors as in younger patients, age-related factors regarding recurrence risk and other-cause mortality are not considered. Genomic risk assessment could help identify patients with ultralow risk BC who can forgo adjuvant treatment. However, assessment tools should be validated specifically for older patients. This study aims to determine whether the 70-gene signature test (MammaPrint) can identify patients with HR + BC aged ≥70 years with ultralow risk for distant recurrence.Materials and MethodsInclusion criteria: ≥70 years; invasive HR + BC; T1-2N0-3M0. Exclusion criteria: HER2 + BC; neoadjuvant therapy. MammaPrint assays were performed following standardized protocols. Clinical risk was determined with St. Gallen risk classification.Primary endpoint was 10-year cumulative incidence rate of distant recurrence in relation to genomic risk. Subdistribution hazard ratios (sHR) were estimated from Fine and Gray analyses. Multivariate analyses were adjusted for adjuvant endocrine therapy and clinical risk.ResultsThis study included 418 patients, median age 78 years (interquartile range [IQR] 73–83). Sixty percent of patients were treated with endocrine therapy. MammaPrint classified 50 patients as MammaPrint-ultralow, 224 patients as MammaPrint-low, and 144 patients as MammaPrint-high risk. Regarding clinical risk, 50 patients were classified low, 237 intermediate, and 131 high. Discordance was observed between clinical and genomic risk in 14 MammaPrint-ultralow risk patients who were high clinical risk, and 84 patients who were MammaPrint-high risk, but low or intermediate clinical risk. Median follow-up was 9.2 years (IQR 7.9–10.5).The 10-year distant recurrence rate was 17% (95% confidence interval [CI] 11–23) in MammaPrint-high risk patients, 8% (4–12) in MammaPrint-low (HR 0.46; 95%CI 0.25–0.84), and 2% (0–6) in MammaPrint-ultralow risk patients (HR 0.11; 95%CI 0.02–0.81). After adjustment for clinical risk and endocrine therapy, MammaPrint-high risk patients still had significantly higher 10-year distant recurrence rate than MammaPrint-low (sHR 0.49; 95%CI 0.26–0.90) and MammaPrint-ultralow patients (sHR 0.12; 95%CI 0.02–0.85). Of the 14 MammaPrint-ultralow, high clinical risk patients none developed a distant recurrence.DiscussionThese data add to the evidence validating MammaPrint's ultralow risk threshold. Even in high clinical risk patients, MammaPrint-ultralow risk patients remained recurrence-free ten years after diagnosis. These findings justify future studies into using MammaPrint to individualize adjuvant treatment in older patients.     

Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort

ObjectivesEffectiveness of bevacizumab for metastatic colorectal cancer in elderly patients has been investigated in observational studies, mainly associated with oxaliplatin-based regimens. Here, using the ETNA cohort in which the majority of patients received bevacizumab + FOLFIRI, the effectiveness of this combination in elderly patients is explored.Materials and MethodsPatients initiating first-line therapy with bevacizumab between January 2006 and December 2007 were identified in 28 French centres and followed for 24 months. Vital status was collected over 36 months. In the present analysis those who received FOLFIRI were retained (85% of those included), and patients were stratified by age (< 70/≥70 years). The Kaplan–Meier method estimated progression-free survival (PFS) and overall survival (OS), and Cox models were used to assess the independent effect of age on survival outcomes.ResultsAmong the 351 patients who received bevacizumab + FOLFIRI, 33.9% were aged ≥ 70 years, 66.1% < 70 years. Respectively 15.1% and 9.5% of patients had ECOG-PS ≥ 2; 49.6% and 40.1% used ‘stop-and-go’ treatment scheduling; and 56.3% and 44.4% experienced grade 3/4 adverse events. Overall response rate was 58.8% and 62.5%. Median [95% confidence interval, CI] OS was respectively 24.1 [20.4; 26.2] and 28.5 [25.0; 31.0] months; age ≥ 70 years and ECOG-PS ≥ 2 were significantly associated with death. Median PFS [95% CI] was respectively 10.9 [9.4; 12.6] and 9.8 [9.2; 11.2] months; hepatic metastases was associated with progression, and age ≥ 70 years was associated with progression after 14 months of follow-up but not before.ConclusionsThe present study adds to the literature on the safe and beneficial effect of bevacizumab in the elderly receiving FOLFIRI regimen.