Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype

Background

Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer.

Methods

Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method.

Results

Of 132 MBC patients, those with heterologous mesenchymal MBC (n?=?45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78–0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32–0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6–3.3; p?<?0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response.

Conclusions

Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC’s unique biology.

     

Second primary malignancies in renal cortical neoplasms: an updated evaluation from a single institution

Purpose

To examine the incidence of secondary primary malignancies in patients with renal cortical neoplasms.

Methods

Between January 1989 and July 2010, 3647 patients underwent surgery at our institution for a renal cortical neoplasm and were followed through 2012. Occurrence of other malignancies was classified as antecedent, synchronous, or subsequent. All patients with antecedent malignancies (n = 498) and a randomly selected half of those with synchronous malignancies (n = 83) were excluded. The expected number of second primaries was calculated by multiplying Surveillance, Epidemiology, and End Results Program incidence rates of renal cortical neoplasms by person-years at risk within categories of age, sex, and year of diagnosis. The standardized incidence ratio (SIR) was calculated as observed cancers divided by expected incidence of the cancer, with approximation to the exact Poisson test used to obtain confidence intervals (CI) and p values.

Results

Of 3066 patients with renal cortical neoplasms, 267 had a second primary cancer; the five most common in men were prostate, colorectal, bladder, lung, and non-Hodgkin’s lymphoma; the five most common in women were breast, colorectal, lung, endometrium, and thyroid. Men demonstrated higher than expected thyroid cancer rate (SIR 5.0; 95 % CI 1.83–10.88, p = 0.002), and women had higher than expected rates of stomach cancer (SIR 5.0; 95 % CI 1.61–11.67, p = 0.004) and thyroid cancer (SIR 4.62; 95 % CI 1.69–10.05, p = 0.003).

Conclusions

The incidence of certain types of second malignancies may be higher in patients after diagnosis of renal cortical neoplasms compared to the general population. These observations can inform clinical follow-up in kidney cancer survivorship and future research studies.

     

Modeling the Cost-Effectiveness of Adjuvant Osimertinib for Patients with Resected EGFR-mutant Non-Small Cell Lung Cancer

IntroductionThe epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib was recently approved for resected EGFR-mutant stages IB-IIIA non-small cell lung cancer due to improved disease-free survival (DFS) in this population compared with placebo. This study aimed to evaluate the cost-effectiveness (CE) of this strategy.Materials and MethodsWe constructed a Markov model using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of 3 years of adjuvant osimertinib versus placebo over a 10-year time horizon. An overall survival (OS) benefit of 5% was assumed. Costs and utility values were derived from Medicare reimbursement data and literature. A CE threshold of 3 times the gross domestic product per capita was used. Sensitivity analyses were performed.ResultsThe incremental cost-effectiveness ratio for adjuvant osimertinib was $317 119 per QALY-gained versus placebo. Initial costs of osimertinib are higher in years 1-3. Costs due to progressive disease (PD) are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2388, $379 047, and $502 937, respectively, in the placebo group, and $505 775, $255 638, and $800 697, respectively, in the osimertinib group. Sensitivity analysis of OS gains reaches CE with an hazard ratio (HR) of 0.70-0.75 benefit of osimertinib over placebo. A 50% discount to osimertinib drug cost yielded an ICER of $115 419.ConclusionsThree-years of adjuvant osimertinib is CE if one is willing to pay $317 119 more per QALY-gained. Considerable OS benefit over placebo or other economic interventions will be needed to reach CE.     

Does response to neo‐adjuvant chemotherapy impact breast reconstruction?

Neo‐adjuvant chemotherapy (NAC) is administered in breast cancer treatment for downstaging of disease. Here, we determined the impact of response to NAC on breast reconstruction uptake. A prospective NAC and mastectomy database with or without reconstruction were reviewed with IRB approval. Univariable analyses were conducted using Kruskal‐Wallis or Fisher's exact tests. Multivariable logistic regression was used to adjust for potential confounders. We identified 271 patients with unilateral breast cancer receiving NAC and either unilateral or bilateral mastectomy from 9/2013 to 5/2016. Seventy patients (25.8%) had a pCR to NAC. One hundred and seventy‐five patients (64.6%) had immediate reconstruction (IR), and 96 had no IR. On univariable analysis, younger age (P < .001), lower T‐stage at presentation (P < .001), bilateral versus unilateral mastectomy (P<.001) and HR‐negative tumor subtype (P = .006) were significantly associated with higher IR rates. On multivariable analysis, pCR (P = .792) and tumor subtype (P = 0.061) were not significantly associated with IR; T‐stage was significantly associated with IR (P < .001), such that patients with T4 tumors at presentation had lower odds of IR (OR 0.10, 95% CI 0.02‐0.50), even when accounting for response to NAC. One hundred and seventy‐three patients (63.8%) received adjuvant radiation therapy; this was associated with lower IR frequency (P = .048) but was not associated with reconstruction type (tissue expander versus autologous, P = 1.0) among 175 patients who had IR. In patients who have mastectomy after NAC, IR is influenced by age, T‐stage at presentation, and choice of bilateral mastectomy, but not by response to NAC. A subset of patients who are young, with earlier T‐stage and pCR, is more likely to proceed with bilateral mastectomy.     

Influence of Age on the Clinical Outcome of Breast Cancer for Men and the Development of Second Primary Cancers

Background

Low incidence of breast cancer in men (BCM) (<?1% of all breast cancers) has led to a paucity of outcome data. This study evaluated the impact of age on BCM outcomes.

Methods

For this study, BCM patients treated between 2000 and 2011 were stratified by age (≤?65 or?>?65 years). Kaplan–Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk.

Results

The study identified 152 BCM patients with a median age of 64 years (range 19–96 years). The median body mass index (BMI) was 28 kg/m². Men age 65 years or younger (n?=?78, 51%) were more overweight/obese than men older than 65 years (n?=?74, 49%) (89% vs 74%, respectively; P?=?0.008). Both groups had similar nodal metastases rates (P?=?0.4), estrogen receptor positivity (P?=?1), and human epidermal growth factor receptor 2 (HER2)neu overexpression (P?=?0.6). Men 65 years of age or younger were more likely to receive chemotherapy (P?=?0.002). The median follow-up period was 5.8 years (range 0.1–14.4 years). The 5-year OS was 86% (95% confidence interval [CI] 80–93%), whereas the 5-year BCSS was 95% (95% CI 91–99%). The BCM patients 65 years of age and younger had better OS (P?=?0.003) but not BCSS (P?=?0.8). The 5-year cumulative incidence of SPC was 8.4% (95% CI 3.4–13.4%). The prior SPC rate was higher for men older than 65 years (n?=?20, 31%) than for those age 65 years or younger (n?=?7, 11%) (P?=?0.008). This did not account for differences in life years at risk. No difference was observed in SPC cumulative incidence stratified by age (P?=?0.3).

Conclusions

Men 65 years of age or younger received more chemotherapy and had improved OS, but not BCSS, compared with men older than 65 years. For all BCM, SPC is a risk, and appropriate screening may be warranted.

     

The Safety and Efficacy of Single‐Agent Pemetrexed in Platinum‐Resistant Advanced Urothelial Carcinoma: A Large Single‐Institution Experience

Background.

Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance.

Patients and Methods.

Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.

Results.

One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%–9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival.

Conclusion.

This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.