Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer.

BACKGROUND: In recent years survival of patients with metastatic colorectal cancer (mCRC), though still limited, has improved significantly; clearly, when the disease becomes refractory to standard regimens, additional treatment options are needed. Studies have shown that mitomycin C (MMC), an antitumor antibiotic, and capecitabine, a precursor of 5-fluorouracil, may act synergistically in combination. The efficacy of MMC/capecitabine has been demonstrated in the first-line setting, but only a few small studies have tested it in the advanced-line setting, with contradictory results. AIM: To summarize our experience using MMC/capecitabine as an advanced line treatment for mCRC. METHODS: A retrospective study was conducted at a tertiary medical center including all patients with histologically proven mCRC who were treated with MMC/capecitabine after at least two previous lines of standard chemotherapy in 2006-2020. Data on patient demographics and past medical history, laboratory, pathological, and radiological factors, and treatment and survival were collected from the files. Survival analyses were performed using the Kaplan-Meier method. The association of patient and tumor characteristics with treatment effectiveness and toxicity was evaluated with univariate and multivariate proportional hazard Cox regression analyses. P ≤ 0.05 was considered statistically significant. RESULTS: The cohort consisted of 119 patients of median age 64 years (range 37-85). Patients received a median of 2 MMC/capecitabine cycles (range 0.5-9.0). Thirty-four patients (28.6%) experienced grade ≥ 3 toxicity, including 2 (1.7%) with grade 4; there was no drug-related mortality. The objective response rate was 0.8%, and the disease control rate, 24.4%. Median progression-free survival (PFS) was 2.1 mo (range 0.2-20.3), and median overall survival, 4.8 mo (range 0.2-27.5). The 6-month overall survival rate was 44%; 8.7% of patients remained progression-free. Factors associated with longer PFS were lower gamma-glutamyl transferase level (P = 0.030) and primary tumor location in the left colon (P = 0.017). Factors associated with longer overall survival were lower gamma-glutamyl transferase level (P = 0.022), left-colon tumor location (P = 0.044), low-to-moderate histological grade (P = 0.012), Eastern Cooperative Oncology Group performance status 0-1 (P = 0.036), and normal bilirubin level (P = 0.047). CONCLUSION: MMC/capecitabine is an active, available, and relatively safe regimen for use beyond standard lines of therapy in mCRC. Several clinical and laboratory parameters can identify patients more likely to benefit.

Differences in Toxicity Between Ashkenazi and Sephardic Jews With Colon Cancer Treated With Adjuvant Chemotherapy: A Prospective Study.

BACKGROUND/AIM: Ethnicity of cancer patients is increasingly being recognized as an important factor that may influence intergroup variation in toxicity and efficacy of chemotherapy. Data from our institution suggested that differences in chemotherapy-associated toxicity are not limited to distanced ethnic subgroups, such as Caucasians, Afro-Americans, or Asians, but may exist even between two closely related Caucasian ethnic subgroups, such as Ashkenazi and Sephardic Jews. This study aimed to explore differences in severity and frequency of various side effects, including neurotoxicity between patients from the two Jewish subgroups receiving oxaliplatin-containing adjuvant chemotherapy for colon cancer (CC). PATIENTS AND METHODS: We recruited 75 patients, with performance status 0-1 and no background of neuropathy between 2012 and 2016. All patients completed a neurotoxicity questionnaire (NQ) and a QoL questionnaire (QoLQ) at baseline and the NQ also at each treatment cycle; during follow up, patients filled out the NQ and the QoLQ every four months for a total of one year. RESULTS: Of the 75 participants, 66 were evaluable for the study including 34 (52%) Sephardic and 32 (48%) Ashkenazi Jews. Grade ≥2 vomiting and diarrhea occurred more often in Sephardic than in Ashkenazi patients (p=0.008 and 0.012, respectively). Of the 66 evaluable patients, 11 (17%) developed grade 3 neurotoxicity; of these, 9 were Sephardic and 2 were Ashkenazi (p=0.028). There were no significant differences in the dynamics of QoL between both subgroups. CONCLUSION: Sephardic patients receiving oxaliplatin-containing regimens are at an increased risk for neurotoxicity and other side effects as compared to their Ashkenazi counterparts.

Strong Synergic Growth Inhibition and Death Induction of Cancer Cells by Astragalus membranaceus and Vaccaria hispanica Extract.

We present here a new, classification-based screening method for anti-cancer botanical combinations. Using this method, we discovered that the combination of Astragalus membranaceus and Vaccaria hispanica (AV) has strong synergic anti-proliferative and killing effects on cancer cells. We showed that AV induces the hyper activation of proliferation and survival pathways (Akt and ERK1/2) and strongly downregulates the cell cycle control proteins p21 and p27. Moreover, FACS analyses revealed that AV induces accumulation of cells in G2/M phase, supported by accumulation of cyclin A. Taken together, our results suggest that AV interferes with the cell cycle in cancer cells, leading to accumulation in G2/M and apoptosis. Further studies are needed to validate the generalizability of the anti-cancer effect of the AV combination, to fully understand its mechanism of action and to evaluate its potential as a new anti-cancer treatment.

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study.

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen. Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD). Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)]. Conclusions: Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study.

BACKGROUND: The combination of a taxane with trastuzumab and pertuzumab is standard of care for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The combination of vinorelbine with trastuzumab and pertuzumab showed anti-tumor activity in a phase 2 trial. PATIENTS AND METHODS: The databases of two tertiary medical centers were retrospectively searched for patients with HER2-positive metastatic breast cancer who underwent first-line treatment in 2013-2019 with a taxane or vinorelbine in combination with trastuzumab and pertuzumab. Groups were compared for progression-free survival (PFS), overall survival (OS), and toxicity profile. RESULTS: The study included 87 patients in the taxane group and 65 in the vinorelbine group. Overall median PFS was significantly longer in the taxane group [HR 0.56 (0.36-0.88), P = 0.01], but on multivariate analysis the difference was not statistically significant [HR 0.68 (0.4-1.1, P = 0.11)]. PFS was comparable in both groups of patients with recurrent disease [HR 0.94 (0.5-1.79), P = 0.85]. However, in patients with de novo metastatic disease, the difference in favor of the taxane group was pronounced [HR 0.4 (0.2-0.78), P = 0.007] and maintained significance on multivariate analysis [HR 0.46 (0.2-0.97, P = 0.04)]. There was no statistical significant difference in OS in the whole cohort [HR 0.69 (0.39-1.23)] or the subgroups. CONCLUSIONS: Patients with HER2-positive metastatic breast cancer had similar survival with first-line treatment of taxane or vinorelbine combined with trastuzumab and pertuzumab. When the analysis was adjusted for prognostic factors, there was no PFS benefit for taxanes except in the subgroup with de novo disease.

ERBB2 Pathway in Biliary Tract Carcinoma: Clinical Implications of a Targetable Pathway.

BACKGROUND/AIMS: Current chemotherapy regimens for cholangiocarcinoma (CCA) yield poor outcomes, with a median overall survival of <12 months. Recent data on the genomic landscape of CCAs have created opportunities for targeted therapy. Yet, data regarding its efficacy are scarce. We aimed to describe the genomic landscape of a CCA patient cohort using next-generation sequencing (NGS), focusing on the ERBB/EFGR pathway and assessing response to anti-HER2 agents. METHODS: Tissue samples of intrahepatic CCA (IHCC) and extrahepatic CCA (EHCC) underwent NGS for somatic aberrations. The clinical outcomes for patients treated with anti-HER2 agents were evaluated. RESULTS: A total of 1,863 CCA cases (1,615 IHCCs and 248 EHCCs) underwent NGS, and they revealed a high prevalence of ERBB alterations (IHCC, 4.2%; EHCC, 9.7%). Among these, 23.8% of the IHCCs and 53.6% of the EHCCs had a point mutation in ERBB2, and 66.6% of the IHCCs and 41.2% of the EHCCs had ERBB copy number amplification. Three EHCC patients were diagnosed at our institute with ERBB/EGFR aberrations; 2 patients were treated with neratinib and 1 patient with a chemotherapy-trastuzumab combination. All 3 achieved disease stabilization and a clinical benefit. One patient underwent a liquid biopsy before and after 3 months of treatment, demonstrating disappearance of the ERBB2 clone and emergence of a Myc-mutated clone after treatment. CONCLUSIONS: The genomic landscape of CCAs may harbor targetable alterations, especially in the ERBB/EGFR pathway. These alterations may have clinical significance in everyday practice.

Prospective Long-Term Follow-Up of Pulmonary Diffusion Capacity Reduction Caused by Dose-Dense Chemotherapy in Patients with Breast Cancer.

BACKGROUND: Our previous study of pulmonary function in 34 patients with early breast cancer without preexisting lung disease showed that anthracycline- and taxane-based adjuvant dose-dense chemotherapy (DDC) caused a significant 16.4% mean reduction in carbon monoxide diffusing capacity (DLCO). The present study reports the pulmonary and oncological outcomes of these patients on long-term follow-up. PATIENTS AND METHODS: The primary endpoint was DLCO measured by the pulmonary function test (PFT) performed at a median of 27 months after DDC (range, 8-97) in 25 patients without disease recurrence. DLCO values were recorded as a percentage of predicted values according to age, height, and hemoglobin level and analyzed relative to baseline pre-DDC DLCO values. The secondary endpoints were symptoms, additional therapies, and cancer outcomes during a median of 11 years' follow-up (range, 4.4-11.4). RESULTS: A longitudinal general linear model showed significant effects of time on DLCO and its trend (F(1, 87) = 14.68, p < 0.001 and F(1, 87) = 10.26, p=0.002, respectively). Complementary descriptive analysis showed a significant recovery on the follow-up PFT (75.6% vs. 81.9%, p=0.002), but it was still significantly lower than the baseline DLCO (81.9% vs. 92.0%, p=0.003). Five patients (20%) still showed a >20% relative DLCO reduction from baseline. Patients with dyspnea or fatigue at later clinical follow-up had a significantly lower DLCO value on the follow-up PFT than nonsymptomatic patients (80.5% vs. 92.1%, p=0.02). DLCO recovery was inversely correlated with age (R = -0.39, p=0.05), but no significant correlation was found with the length of time until the follow-up PFT or additional therapies. There was no association of DDC-related DLCO reduction with cancer outcomes. CONCLUSIONS: The significant reduction in DLCO seen after DDC in patients with potentially curable breast cancer is evident years afterwards, especially in older patients. While most patients partly recover, some will have a lasting symptomatic DLCO impairment.

The addition of cetuximab to preoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rate of long term survival: Mature results from a prospective phase Ib/II trial.

AIM: This phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative chemoradiotherapy (CRT) in locally advanced esophageal cancer (LAEC). METHODS: Patients (pts) with resectable LAEC (T2-3N0-1M0, T1-3N1M0 or T1-3N0-1M1A) received an induction cycle of cisplatin 100 mg/m2, day 1, and 5-fluorouracil (5-FU) 1000 mg/m2/day, days 1-5, followed 4 weeks later by radiotherapy, 50.4 Gy, given with 2 cycles of cisplatin 75 mg/m2 and escalating doses of 5-FU, days 1-4 and 29-32. Pts received 10 weekly infusions of cetuximab, 250 mg/m2, with a loading dose, 400 mg/m2. Surgery was planned 6-8 weeks after CRT. RESULTS: 64 pts were treated and 60 completed CRT. Median age was 65 years and 66% were males. Adenocarcinoma/squamous ratio was 61%/39%. Tumors were advanced: 95% T3 and 67% N1. Grade ≥3 toxicities occurred in 72%, with two (3%) toxic deaths. The 5-FU maximal tolerated dose (MTD) was 1000 mg/m2/day. Clinical complete response rate was 33%. Of the 55 operated pts, R0 resection was achieved in 51 (93%) and pathological complete response (pCR) in 18 (33%), with 8 (14%) postoperative deaths. The 5-year survival rate for all pts was 38%. Pts with squamous histology had higher pCR (55% vs 20%, p = 0.015), local control (96% vs. 74%, p < 0.001) and 5-year survival (58% vs 25%, p = 0.011) rates. CONCLUSIONS: This study suggests that the addition of cetuximab to standard preoperative CRT is feasible. R0, pCR and local control rates are encouraging. Pts with squamous cell tumors benefited more from the addition of cetuximab.

Prognostic Value of the Detection of Lymphovascular Invasion in Hormone Receptor-Positive Early Breast Cancer in the Era of Molecular Profiling.

BACKGROUND: Lymphovascular invasion (LVI) is considered a negative prognostic factor in early breast cancer, but its role in decision-making regarding adjuvant chemotherapy is unclear in the current era of molecular profiling. This study sought to evaluate the association of LVI status with the recurrence score (RS) on the multigene Oncotype DX (ODX) assay and its impact on outcome. METHODS: Patients with early estrogen receptor-positive breast cancer who underwent ODX analysis in 2005-2012 were retrospectively identified. Clinical data were collected from the medical records. The Cox proportional-hazards ratio was used to determine recurrence rates. The prognostic significance of LVI was evaluated by competing risks analysis. RESULTS: LVI was detected in 38 of 657 patients (6%). LVI was not associated with ODX RS (p = 0.225). However, it was significantly associated with other known prognostic factors and with worse 5-year disease-free survival (HR 2.93; 95% CI 1.02-8.39; p = 0.04). Overall survival (OS) analysis according to the ODX subgroups showed that the presence of LVI was associated with worse 5-year OS (p = 0.04) only in the intermediate-risk group, while LVI had no effect on the low- or high-risk groups. CONCLUSIONS: Although LVI was not significantly associated with a higher ODX RS, it may infer a worse outcome, especially in ODX intermediate-risk patients.

Early PET-CT in patients with pathological stage III colon cancer may improve their outcome: Results from a large retrospective study.

BACKGROUND: Current staging of pathological stage III colon cancer (CC) is suboptimal; many patients recur despite unremarkable preoperative staging. We previously reported that early postoperative PET-CT can alter the stage and management of up to 15% of patients with high-risk stage III CC. This study aimed to determine the role of the test in the general stage III CC population. METHODS: A retrospective study of all consecutive patients with stage III CC who underwent early postoperative PET-CT between 2005 and 2017. RESULTS: A total of 342 patients, 166 (48.5%) males, median age 66 years (range, 29-90), were included. Pathological stage was IIIA, IIIB, and IIIC in 18 (5.3%), 257 (75.1%), and 67 (19.6%) patients, respectively. Median number of positive lymph nodes was 2 (range, 0-32). PET-CT results modified the management of 46 patients (13.4%): 37 (10.8%) with overt metastatic disease and 9 (2.6%) with a second primary. The 5-year disease-free survival for true stage III patients was 81%. The median overall survival for the entire cohort and for true stage III patients was not reached and was 57.2 months for true stage IV. Of the 37 patients found to be metastatic, 14 (37.8%) underwent curative treatments and 9/14 (64.3%) remain disease-free, with a median follow-up of 83.8 months. Predictive factors for upstaging following PET-CT were identified. CONCLUSION: Early postoperative PET-CT changed the staging and treatment of 13.4% of stage III CC patients and has the potential for early detection of curable metastatic disease. Outcome results are encouraging. Prospective validation is ongoing.

Early Breast Cancer in the Elderly: Characteristics, Therapy, and Long-Term Outcome.

OBJECTIVE: The number of older adults diagnosed with breast cancer is increasing. However, data on breast cancer characteristics, treatment, and survival in elderly women are sparse. METHODS: The database of a tertiary cancer center was searched for all women aged ≥65 years who were diagnosed with early breast cancer in 2004-2007. Patients were divided into 2 age groups: 65-75 years and >75 years. Data on tumor, treatment, and outcome parameters were compared. RESULTS: The cohort included 390 patients. The older group underwent more mastectomies but less axillary surgery or adjuvant systemic therapy. Median overall survival (OS) was 9.5 years in the older group and not reached in the younger group; the 8-year disease-free survival rates were 85 and 88%, respectively (p = 0.27). Both age and tumor subtype had an effect on OS and recurrence rates (p < 0.001 for OS; p = 0.16 for recurrence). The worst outcome was noted in women aged >75 years with triple-negative (TN) disease. CONCLUSION: The treatment approach was different between both age groups, despite similar tumor characteristics. TN subtype presented as the most aggressive disease in both age groups. Physicians should be alert to these findings and select treatment on a case-by-case basis.

Molecular Predictors of Response to Neoadjuvant Chemoradiation for Rectal Cancer.

OBJECTIVES: To determine whether the expression of specific molecular markers in the rectal cancer biopsies prior to treatment, can correlate with complete tumor response to chemoradiotherapy (CRT) as determined by the pathology of the surgical specimen. METHODS: We retrospectively examined pretreatment rectal biopsies of patients aged 18 years or older with locally advanced rectal cancer who had been treated with neoadjuvant CRT and surgical resection in our tertiary-care, university-affiliated medical center, between January 2001 and December 2011. Samples were analyzed for expression of B-cell lymphoma 2, P53, Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor, and the tumor regression grade after CRT and radical surgery. RESULTS: Forty-seven patients were included in the final analysis. Main outcome measures were the correlation between the expression of the molecular markers tested in the pretreatment biopsy, and complete tumor response. Complete pathologic response after CRT was attained in 27% of the patients. Percentage of cells expressing EGFR in the pretreated biopsies of patients having complete pathologic response after CRT and surgery was 33.08±7.87% compared to 19±15.36% (P=0.38), 6.66±2.83% (P<0.003), and 12.5±4.93% (P=0.033) in patients with partial response and tumor regression grades of 2, 3, and 4, respectively. The other molecular markers tested in the pretreatment biopsy did not corresponded with complete pathologic response. CONCLUSIONS: EGFR expression pattern in the pretreatment biopsies of rectal tumors can assist in identifying patients who will benefit from neoadjuvant CRT.

The association between smoking and breast cancer characteristics and outcome.

BACKGROUND: Smoking is associated with an increased incidence of hormone receptor positive breast cancer. Data regarding worse breast cancer outcome in smokers are accumulating. Current literature regarding the impact of smoking on breast cancer characteristics is limited. We evaluated the impact of smoking on breast cancer characteristics and outcome. METHODS: This was a retrospective single center study. All women diagnosed from 4/2005 through 3/2012 and treated in our institute for early, estrogen receptor positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer, whose tumors were sent for Oncotype DX analysis were included. Medical records were reviewed for demographics, clinico-pathological parameters, treatment and outcome. Data regarding smoking were retrieved according to patients' history at the first visit in the oncology clinic. Patients were grouped and compared according to smoking history (ever smokers vs. never smokers), smoking status (current vs. former and never smokers) and smoking intensity (pack years ≥30 vs. the rest of the cohort). Outcomes were adjusted in multivariate analyses and included age, menopausal status, ethnicity, tumor size, nodal status and grade. RESULTS: A total of 662 women were included. 28.2% had a history of smoking, 16.6% were current smokers and 11.3% were heavy smokers. Smoking had no impact on tumor size, nodal involvement and Oncotype DX recurrence score. Angiolymphatic and perineural invasion rates were higher in current smokers than in the rest of the cohort (10.4% vs. 5.1%, p = 0.045, 8.3% vs. 3.5%, p = 0.031, respectively). Smoking had no other impact on histological characteristics. Five-year disease free survival and overall survival rates were 95.7% and 98.5%, respectively. Smoking had no impact on outcomes. Adjusted disease free survival and overall survival did not influence the results. CONCLUSIONS: Smoking had no clinically significant influence on tumor characteristics and outcome among women with estrogen receptor positive, HER2 negative, early breast cancer. As the study was limited to a specific subgroup of the breast cancer population in this heterogeneous disease and since smoking is a modifiable risk factor for the disease, further research is required to clarify the possible impact of smoking on breast cancer.

Esophageal Cancer in Israel has Unique Clinico-Pathological Features: A Retrospective Study.

Introduction: Data regarding esophageal cancer (EC) in Israel are limited. The aim of this study was hence to characterize this entity in the Israeli population and to compare it to the literature. Patients/Methods: This is a retrospective study of all consecutive EC patients treated at our institution between 1997-2013. Data were retrieved from patients' medical files. Results: Two hundred patients were included. The median age at diagnosis was 70.5 years; 63.5% were males; 63% were Ashkenazi Jews, 29% were Sephardic Jews, and 0.5% were Arabs. Squamous cell carcinoma (SCC) was predominant: 52% versus 45.5% with adenocarcinoma (ADC). SCC was common even in the distal esophagus (45%). The overall 5-year survival rate was 25.5%. A temporal trend (2006-2013 vs 1997-2005) shows a decline in the proportion of SCC (47% vs 63%, p=0.061) and a rise in ADC (50% vs 33%, p=0.041), with a parallel decrease in patients' age (median: 68.5 vs 73 years, p=0.014). In the later period, patients received more treatment for localized and metastatic disease, with a trend for improved median survival (20.1 vs 14.9 months, p=0.658). Ashkenazi Jews were diagnosed at an older age than Sephardic Jews (median: 73 vs. 65 years, p=0.001), had a higher rate of family history of GI cancer (34% vs. 17%, p=0.026) and a higher rate of cardiovascular co-morbidity (41% vs. 24%, p=0.041). Conclusion: EC in Israel represents an intermediate entity between the Western and the endemic subtypes, showing some unique features. These included delayed reversal of the SCC/ADC ratio, commonness of SCC in the distal esophagus, prevalence of other malignancies and predominance of Ashkenazi ethnicity. The reason for these findings is unclear and its further evaluation is warranted.

Octogenarian patients with colorectal cancer: Characterizing an emerging clinical entity.

AIM: To characterize colorectal cancer (CRC) in octogenarians as compared with younger patients. METHODS: A single-center, retrospective cohort study which included patients diagnosed with CRC at the age of 80 years or older between 2008-2013. A control group included consecutive patients younger than 80 years diagnosed with CRC during the same period. Clinicopathological characteristics, treatment and outcome were compared between the groups. Fisher's exact test was used for dichotomous variables and χ2 was used for variables with more than two categories. Overall survival was assessed by Kaplan-Meier survival analysis, with the log-rank test. Cancer specific survival (CSS) and disease-free survival were assessed by the Cox proportional hazards model, with the Fine and Gray correction for non-cancer death as a competing risk. RESULTS: The study included 350 patients, 175 patients in each group. Median follow-up was 40.2 mo (range 1.8-97.5). Several significant differences were noted. Octogenarians had a higher proportion of Ashkenazi ethnicity (64.8% vs 47.9%, P < 0.001), a higher rate of personal history of other malignancies (22.4% vs 13.7%, P = 0.035) and lower rates of family history of any cancer (36.6% vs 64.6%, P < 0.001) and family history of CRC (14.4% vs 27.3%, P = 0.006). CRC diagnosis by screening was less frequent in octogenarians (5.7% vs 20%, P < 0.001) and presentation with performance status (PS) of 0-1 was less common in octogenarians (71% vs 93.9%, P < 0.001). Octogenarians were more likely to have tumors located in the right colon (45.7% vs 34.3%, P = 0.029) and had a lower prevalence of well differentiated histology (10.4% vs 19.3%, P = 0.025). They received less treatment and treatment was less aggressive, both in patients with metastatic and non-metastatic disease, regardless of PS. Their 5-year CSS was worse (63.4% vs 77.6%, P = 0.009), both for metastatic (21% vs 43%, P = 0.03) and for non-metastatic disease (76% vs 88%, P = 0.028). CONCLUSION: Octogenarians presented with several distinct characteristics and had worse outcome. Further research is warranted to better define this growing population.

The Association between Treatment for Metabolic Disorders and Breast Cancer Characteristics.

Purpose. To evaluate the associations between metformin, insulin, statins, and levothyroxine and breast cancer characteristics and outcome. Methods. Retrospective chart review of patients treated in our institute for early estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative breast cancer, whose tumors were sent to Oncotype DX (ODX) analysis. Patients were grouped according to medications usage during the time of breast cancer diagnosis. Each group was compared to the rest of the study population. Results. The study cohort included 671 patients. Sixty (9.1%) patients were treated with metformin, 9 (1.4%) with insulin, 208 (31.7%) with statins, and 62 (9.4%) with levothyroxine. Patients treated with metformin had more intense ER stain (p = 0.032) and a lower ODX recurrence score (RS) (p = 0.035). Diagnosis of diabetes mellitus was also associated with lower ODX RS (p = 0.014). Insulin usage was associated with a higher rate of angiolymphatic invasion (p = 0.041), but lower Ki67% (p = 0.017). Levothyroxine usage was associated with different histological subtype distribution (p = 0.02). Extended levothyroxine usage was associated with lower ODX RS (p = 0.005). Statin usage had no impact on tumor characteristics. Outcome was comparable in the studied subgroups. Conclusions. Common medications for metabolic disorders might be associated with breast cancer characteristics.

Earlier Age of Breast Cancer Onset in Israeli BRCA Carriers-Is it a Real Phenomenon?

Data on genetic anticipation in breast cancer are sparse. We sought to evaluate age at diagnosis of breast cancer in daughters with a BRCA mutation and their mothers. A review of all carriers of the BRCA mutation diagnosed with breast cancer at the Genetics Institute of a tertiary medical center in 2000-2013 yielded 80 women who could be paired with a mother with breast cancer who was either a carrier of the BRCA mutation or an obligate carrier according to pedigree analysis. Age at diagnosis, type of mutation (BRCA1, BRCA2), year of birth, and ethnicity were recorded. Paired t-test was used to analyze differences in age at cancer diagnosis between groups and subgroups. Mean age at diagnosis of breast cancer was 50.74 years (range 22-88) in the mothers and 43.85 years (range 24-75) in the daughters. The difference was statistically significant (p < 0.001). These findings were consistent regardless of type of BRCA mutation, ethnicity, or mother's year of birth. However, on separate analysis of pairs in which the mother was diagnosed before the age of 50 years, there was no significant difference in mean age at diagnosis between mothers and daughters (~42 years for both). Daughters who carry a BRCA mutation are diagnosed with breast cancer at an earlier age than their carrier mothers, with the exception of pairs in which the mother was diagnosed before the age of 50 years. Future breast-screening guidelines may need to target specific subpopulations of BRCA mutation carriers.