Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently ...available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.
We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical IHC analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.
Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.
In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal ...women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
Purpose
Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer, with limited data available regarding treatment and outcomes. This study aims to review patients with MBC ...treated at our tertiary care institution with an emphasis on the role of treatment modality and histologic classification.
Methods
With IRB-approval, we queried our pathology database for patients with MBC diagnosis. All cases were re-evaluated by dedicated breast pathologists and confirmed as MBC breast cancer. Patient demographics, clinical/pathologic histology, and treatment were analyzed with respect to outcomes including local–regional recurrence (LRR), distant metastasis (DM), and overall survival (OS). Univariate and multivariate Cox proportional hazards models were performed to evaluate the impact on outcomes. Kaplan–Meier methods estimated survival.
Results
We evaluated 113 patients with MBC diagnosed between 2002 and 2013. Median age was 61 years and median pathologic tumor size 2.5 cm; 76 (67%) were ER/PR/Her2 negative, 83 (74%) grade 3. Median follow-up was 38 months. 47 (42%) underwent breast conservation therapy (BCT), 66 (58%) had mastectomy, 61 (54%) underwent adjuvant radiation (RT), and 85 (75%) had chemotherapy. At 2 and 5 years, the LRR/DM/OS rates were 12%/15%/90% and 21%/35%/69%, respectively. On Cox regression analysis, only adjuvant RT correlated with reduced LRR RR 3.1 (1.13–9.88),
p
= 0.027, while chemotherapy, type of surgery, and T-N stage did not. Only T-stage (
p
= 0.008) correlated with DM, however chemotherapy, RT, surgery type, and N-stage were not. Univariate analysis demonstrated histologic subtype did not significantly correlate with local (
p
= 0.54) or distant (
p
= 0.83) disease control.
Conclusions
This study represents among the largest institutional experiences in the outcomes of MBC. At this time, there does not appear to be a clear histologic subset of MBC which has significantly different clinical outcomes from the other subtypes. Although limited in its sample size, this study shows RT remains important in local–regional control.
Purpose
Peripheral neuropathy (PN) is a common and distressing complication from chemotherapy. Symptoms often, but not always, improve with time. The prevalence of long-term PN symptoms in breast ...cancer survivors is not well known. We sought to explore PN symptoms and associated risk factors among breast cancer survivors at least 2 years out from diagnosis.
Methods
We performed a cross-sectional retrospective study investigating the prevalence of patient-reported numbness, tingling, and anesthesia symptoms as a surrogate for PN in breast cancer survivors. We included patients with stage 0–III breast cancer who completed a clinical questionnaire at a survivorship visit that occurred 2 or more years after diagnosis. We estimated the prevalence of PN and identified risk factors for PN.
Results
Six hundred and five patients assessed between April 2009 and October 2016 met eligibility for analysis. Median age was 60 years. Median number of years from diagnosis to assessment was 6.3. All patients had surgery and 62% had chemotherapy. Twenty-seven percent reported PN. On univariable analysis, obesity, stage II and III, mastectomy, PN before diagnosis, and receipt of taxane chemotherapy were associated with higher risk of PN (all
p
< 0.05); older age, exercise, ER-positive disease, and endocrine therapy were associated with lower risk of PN (all
p
< 0.05). On multivariable analysis, only receipt of docetaxel (OR 2.18, CI 1.22–3.88) or paclitaxel (OR 4.07, CI 2.54–6.50) and reporting PN symptoms before diagnosis (OR 3.28, CI 1.49–7.21) were associated with higher risk of PN. Overall, 17, 20, 31, and 44% reported long-term PN symptoms after no chemotherapy, non-taxane chemotherapy, docetaxel chemotherapy, and paclitaxel chemotherapy, respectively.
Conclusion
Long-term peripheral neuropathy symptoms are reported by a significant minority of breast cancer survivors, particularly following paclitaxel or docetaxel chemotherapy. These study findings can help inform patients and clinicians regarding long-term PN risk following chemotherapy.
Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking.
We conducted ...a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial.
Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval CI, 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort.
Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).
Chemotherapy can improve prospects for long-term survival after a cancer diagnosis, but it may also be associated with long-term toxicity, including the possibility of cognitive dysfunction. While a ...variety of factors may contribute to cognitive impairment in cancer survivors, there is increasing evidence that chemotherapy contributes to both subjective and objective changes in cognition. These effects appear to be most pronounced in the short-term, with improvement over time expected for most patients. Pharmacologic treatments do not have proven value in the management of chemotherapy-related cognitive dysfunction, but patients may benefit from cognitive rehabilitation. Clinical guidelines are needed for assessment and management of chemotherapy-related cognitive dysfunction.
Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The ...diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.
Purpose
Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of ...cyclin-dependent kinases 4 and 6 that has been shown to improve progression-free survival (PFS) when combined with letrozole or fulvestrant in phase 3 clinical trials. We evaluated real-world outcomes in metastatic breast cancer patients who received palbociclib in combination with endocrine therapy in routine clinical practice.
Methods
Records of patients with advanced hormone receptor (HR)-positive breast cancer treated with palbociclib at the Cleveland Clinic health system from February, 2015 to December, 2017 were retrospectively reviewed. The primary end point was PFS.
Results
In this cohort, 411 women were included. The median age and follow-up times were 53.5 years and 10.2 months, respectively. The median PFS for palbociclib plus letrozole was 15.1 months for patients treated in first line, 10.5 months in second line, and 4.2 months in third line and beyond. For patients who received fulvestrant plus palbociclib, the median PFS in first, second, and third line and beyond were 11.6, 12.3, and 6.4 months, respectively. The most common adverse events were hematologic, with grade 3–4 neutropenia occurring in 58% of patients. Thirty-one (8%) patients permanently discontinued palbociclib due to adverse events.
Conclusions
Among patients with HR-positive advanced breast cancer, the estimated PFS in patients treated with fulvestrant and palbociclib was comparable to a previously reported phase 3 trial. However, the median PFS with letrozole and palbociclib was shorter than previously reported data from phase 2 and 3 trials. Palbociclib toxicity was very manageable, with a low drug discontinuation rate.
Most individuals diagnosed with breast cancer will experience long-term survival. Following initial active treatment for breast cancer, survivors may experience a variety of medical, physical, and ...psychosocial consequences that may affect overall health and wellbeing. Clinicians providing care for breast cancer survivors should be comfortable addressing long-term effects of cancer and its treatment, including cardiovascular toxicity, sequelae of estrogen deficiency, chronic pain, fatigue, cognitive concerns, sleep issues, and psychosocial concerns. In addition, providers should promote health maintaining behaviors including healthy lifestyle, treatment adherence, and appropriate surveillance. Survivorship care should be individualized based on treatment received with regular assessment of active symptoms and comorbidities.
Background
Endocrine therapy reduces recurrence risk and improves survival in women with hormone receptor-positive breast cancer; however, side effects can decrease quality of life, leading to ...reduced treatment adherence. Sarcopenia is the loss of skeletal muscle mass that happens with age; it is associated with worse survival and reduced chemotherapy adherence in patients with breast cancer. The impact of sarcopenia on endocrine therapy tolerance has not been investigated. The current study evaluates the associations of sarcopenia with endocrine therapy toxicity and treatment tolerance.
Methods
Skeletal muscle mass was measured by bioelectrical impedance spectrometry. Skeletal muscle index (SMI) was calculated to assess for sarcopenia: SMI = (SMM kg)/(patient height, m
2
). Patients with SMI ≤ 6.75 kg/m
2
were considered sarcopenic. A chart review was performed to obtain patient characteristics, endocrine therapy toxicity, and early treatment change or termination. Fisher's exact test was performed to associate patient characteristics and outcomes with sarcopenia status.
Results
Four hundred eighty-two patients with stage I–III breast cancer were prescribed endocrine therapy and had undergone sarcopenia evaluation. The median age was 61 years (29–88 years). Sarcopenia was identified in 35% of patients. Twelve percent of patients experienced grade 3–4 endocrine-related toxicities. On multivariable logistic analysis, sarcopenia was associated with increased odds of experiencing endocrine-related side effects (
p
= 0.006). In addition, patients with sarcopenia stopped or changed their medication due to side effects more often than those without sarcopenia (
p
= 0.03).
Conclusion
The presence of sarcopenia in patients with EBC represents a potentially modifiable risk factor for more significant endocrine therapy side effects and reduced treatment tolerance.
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