Cancer stem cells (CSCs) are proposed to initiate cancer and propagate metastasis. Breast CSCs identified by aldehyde dehydrogenase (ALDH) activity are highly tumorigenic in xenograft models. However, in patient breast tumor immunohistological studies, where CSCs are identified by expression of ALDH isoform ALDH1A1, CSC prevalence is not correlative with metastasis, raising some doubt as to the role of CSCs in cancer. We characterized the expression of all 19 ALDH isoforms in patient breast tumor CSCs and breast cancer cell lines by total genome microarray expression analysis, immunofluorescence protein expression studies, and quantitative polymerase chain reaction. These studies revealed that ALDH activity of patient breast tumor CSCs and cell lines correlates best with expression of another isoform, ALDH1A3, not ALDH1A1. We performed shRNA knockdown experiments of the various ALDH isoforms and found that only ALDH1A3 knockdown uniformly reduced ALDH activity of breast cancer cells. Immunohistological studies with fixed patient breast tumor samples revealed that ALDH1A3 expression in patient breast tumors correlates significantly with tumor grade, metastasis, and cancer stage. Our results, therefore, identify ALDH1A3 as a novel CSC marker with potential clinical prognostic applicability, and demonstrate a clear correlation between CSC prevalence and the development of metastatic breast cancer. STEM CELLS 2011;29:32-45 Disclosure of potential conflicts of interest is found at the end of this article.

Lymphedema (LE) is a well-known postoperative complication after axillary node dissection (ALND). Although, sentinel lymph node dissection (SLND) involves more focused surgery and less disruption of the axilla, early reports show up to 13% of patients experience some symptoms of LE. The purpose of this study was to determine predictors of arm LE in our patients under going SLND with or without an ALND. One hundred and thirty-seven breast cancer patients were treated at a comprehensive cancer center. Prospective measurement of arm volume was carried every 6 months from date of diagnosis. This data base was retrospectively reviewed for tumor stage, treatment, and subjective complaints of LE. Objective LE was defined as a change greater than 200 mL compared with the control arm. Univariate and multivariate analyses were performed. Arm volume changes were measured over 24 months (median follow-up 20 months) in 137 women: 82 stage I, 48 stage II, and 5 stage III; median age 56 years. Breast-conserving surgery was performed in 133 patients. All patients underwent SLND for axillary staging and for 52 patients this was the only axillary staging procedure. All node-positive patients (31) and 54 node-negative patients under went an immediate completion ALND, the latter as part of a study protocol. At 24 months, 16 (11.6%) patients were found to have objective LE (>200 mL increase). Patient age, tumor size, number of nodes harvested, or adjuvant chemotherapy was not found to be predictive of LE by univariate analysis. The risk of developing postoperative LE was primarily and significantly related to the patients' BMI (p = 0.003). Multivariate analysis revealed patients with a BMI >30 (obese) had an odds ratio of 2.93 (95% CI 1.03-8.31) compared with those with a BMI of <25 of having LE. Symptomatic LE (SLE), as defined by patient complaints was recorded in six of the above 16 patients, no SLE was recorded in patients without objective signs of edema. Univariate subgroup analysis compared the symptomatic to the nonsymptomatic patients and revealed the median number of nodes removed was higher in the symptomatic patients (17 verses 9, p = 0.045); however, these patients had a lower BMI (p = 0.0012). The mean change in arm volume was not significantly different between the groups. SLE occurs in one third of patients with objective arm swelling and most likely is multi-factorial in etiology. Although patients undergoing SLN were recorded as having objective LE, none reported SLE. The development of LE within 2 years of surgery is associated with the patient's BMI and this should be considered in preoperative counseling.

Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

BackgroundComplementary and alternative medicine (CAM) use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC).MethodsWomen with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users.ResultsThirty-six patients were approached, 32 completed the questionnaire (response rate 89%). Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4) with vitamins being the most popular (60%). Motivation for CAM therapy was described as, "assisting their body to heal" (75%), to 'boost the immune system' (56%) and to "give a feeling of control with respect to their treatment" (56%). CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%), however the CAM group had less severe anxiety and depression.ConclusionThe motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with conventional therapy. Consequently more research is needed in this ever-growing field.