Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: A prospective paired cohort study

Background: Recent data suggest that tamoxifen may act by altering serum levels of insulin-like growth factors (IGFs) and their binding proteins (BPs). This prospective paired cohort study evaluated the influence of tamoxifen on serum levels of IGFs and BPs in postmenopausal patients with breast cancer. Methods: Blood was collected from 32 postmenopausal patients with breast cancer before and during tamoxifen therapy for at least 6 months. All patients had undergone primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were determined by immunoradiometric assays, and Western ligand blots provided a semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was performed by paired Student'st-test. Results: Mean serum IGF-1 level was significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL±13.6 [SEM] vs. posttreatment: 77.5 ng/mL±7.8;P=.003). In contrast, mean IGF-II levels increased from 651.5±62.2 ng/mL to 812.5±35.1 ng/mL during treatment (P=.006). Posttreatment levels of BP-1 (92.9 ng/mL±7.5) were significantly higher compared to the pretreatment values (28.1 ng/mL±4.7;P<.001). Serum concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL±145.2 vs. posttreatment: 3539.1 ng/mL±172.3;P<.001). Densitometric measurements showed a similar significant increase in BP-3 (P<.001) as well as BP-4 (P=.017) after hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment. Conclusions: These significant alterations in serum concentrations of IGFs and BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.     

Nodal Pathologic Complete Response Rates in Luminal Breast Cancer Vary by Genomic Risk

Background

Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2? breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2? disease.

Methods

Patients with ER+/HER2? clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010–2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0–25, or Mammaprint 70-gene or RS coded as “Low.” High genomic risk included RS >25, or 70-gene or RS coded as “High.” Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression.

Results

Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002).

Conclusions

For patients with node-positive ER+/HER2? breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management.

     

Serum resistin is inversely related to breast cancer risk in premenopausal women

BackgroundAdipokines have been suggested as potential mediators linking obesity and breast cancer. Resistin is the least-studied adipokine with diverse findings regarding its association with disease development and progression. The present study aimed to determine resistin serum levels in breast cancer in relation to the histological type of disease and to investigate their association with breast cancer risk.MethodsThe study included 216 women, of which 163 were diagnosed with breast cancer (58 with IDC, 52 with DCIS and 53 with LN) and 53 were healthy. Serum levels of resistin, leptin and adiponectin were quantitatively determined in duplicates by ELISA. Differences in resistin levels among patient groups were evaluated with Kruskal–Wallis and Mann–Whitney tests. The association of resistin with breast cancer risk was evaluated by multiple logistic regression analysis.ResultsResistin levels varied between histological types of breast cancer (p = 0.044). Significant differences in serum resistin were observed in IDC patients compared to those with DCIS and to controls (p < 0.014 and p < 0.03, respectively). Decreased levels of resistin, adiponectin and leptin were observed in premenopausal patients. Resistin was associated with a reduced risk for ductal carcinoma only in premenopausal women (OR: 0.364, 95% CI: 0.154–0.862, p < 0.022).ConclusionOur findings indicate that resistin levels were inversely related to breast cancer risk in premenopausal women, supporting a protective role of resistin for these patients. Further advances in adipokine research may lead to tangible benefits for overweight/obese women at an increased risk for breast cancer.     

Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis

BackgroundThe role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer.MethodsSystematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model.ResultsSeven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03–4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49–0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23–6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93–7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69–7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33–4.10; p < 0.001).ConclusionsHigh-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer.     

Treatment of Metastatic Breast Cancer With Somatostatin Analogues—A Meta-Analysis

Background: Somatostatin analogues appear to have antiproliferative effects in breast cancer by inhibiting various hormones. Several small phase 1 and 2 clinical trails have evaluated the efficacy of somatostatin analogues, but the results are varied. The purpose of this study was to use the technique of meta-analysis to determine the effect of somatostatin analogues on tumor response, toxicity, and serum hormone levels in women with metastatic breast cancer.Methods: All published and unpublished trials were reviewed. Meta-analysis was preformed by best linear unbiased estimate regression with observations weighted inversely to their variance. Significance was considered at P < .05.Results: Fourteen studies (N = 210) were included. Positive tumor response was reported in 87 patients (41.4%). Mean duration of response was 3.9 months. Response was best when somatostatin analogues were given as first-line therapy (69.5% versus 28.5%, P < .006) and in patients with 2 metastases (45.0% versus 5.6%, P = .3). Mild side effects occurred in 47 of 185 patients (25.4%). Therapy was associated with a decrease in serum insulin-like growth factor (IGF-1) and an increase in growth hormone.Conclusions: In patients with metastatic breast cancer, treatment with somatostatin analogues was associated with a tumor response of over 40% with few side effects. Best results were achieved when somatostatin analogues were given as first-line therapy.     

Undertreatment of Gallbladder Cancer: A Nationwide Analysis

Background

Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer.

Methods

Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004–2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan–Meier and Cox proportional hazard methods.

Results

The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p?<?0.0001), private insurance (41.6% vs 27.1%; p?<?0.0001), academic centers (50.4% vs 29.7%; p?<?0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p?=?0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p?=?0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p?<?0.0001), negative margins on final pathology (90.1% vs 72.6%; p?<?0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p?<?0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p?<?0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p?=?0.0004).

Conclusions

Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.

     

Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet

ObjectiveBreast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet.MethodsWe analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue.ResultsBreast related topics had significantly more posts per day compared to others (mean 66.7, p < 0.01). Most posts were on media sites (65.8%). Accuracy levels were high (87.5%) but significantly lower where posted on blogs and discussion forums (p < 0.001). Anonymous posts were common (55%) and less likely to be accurate (p < 0.001). Use of discussion forums has exponentially increased over the last five years (p < 0.001).ConclusionsThe internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves.     

Incidence of Atypical Femur Fractures in Cancer Patients: The MD Anderson Cancer Center Experience

Atypical femoral fractures (AFFs) are rare adverse events attributed to bisphosphonate (BP) use. Few cases of AFF in cancer have been described; the aim of this study is to identify the incidence and risk factors for AFF in a large cancer center. This retrospective study was conducted at the MD Anderson Cancer Center. The incidence rate of AFF among BP users was calculated from January 1, 2004 through December 31, 2013. The control group (n = 51) included 2 or 3 patients on BPs matched for age (≤1 year) and gender. Logistic regression analysis was used to assess the relationship between clinical characteristics and AFF. Twenty‐three AFF cases were identified radiographically among 10,587 BP users, the total BP exposure was 53,789 months (4482 years), and the incidence of AFF in BP users was 0.05 cases per 100,000 person‐years. Meanwhile, among 300,553 patients who did not receive BPs there were 2 cases of AFF as compared with the 23 cases noted above. The odds ratio (OR) of having AFF in BP users was 355.58 times higher (95% CI, 84.1 to 1501.4, p < 0.0001) than the risk in non‐BP users. The OR of having AFF in alendronate users was 5.54 times greater (OR 5.54 [95% CI, 1.60 to 19.112, p = 0.007]) than the odds of having AFF among other BP users. Patients who were on zoledronic acid (ZOL) had smaller odds of developing AFF compared with other BP users in this matched case control sample. AFFs are rare, serious adverse events that occur in patients with cancer who receive BP therapy. Patients with cancer who receive BPs for prior osteoporosis therapy or for metastatic cancer are at higher risk of AFF. © 2016 American Society for Bone and Mineral Research.     

High Hospital Volume Is Associated with Better Outcomes for Breast Cancer Surgery: Analysis of 233,247 Patients

Background: The relationship between hospital volume and outcomes needs to be further elucidated for low-risk procedures such as surgical therapy of localized breast cancer. The objective of this investigation was to assess the relationship between hospital volume and outcomes for breast cancer surgery. Methods: A total of 233,247 patients who underwent breast-conserving therapy (BCT) and breast-ablative therapy (BAT) for localized breast cancer were extracted from 13 years (1988–2000) of the Nationwide Inpatient Samples. Hospital volume was classified as low (<30 cases/year), intermediate (≥ 30 to <70cases/year), and high (≥ 70 cases/year). Multiple linear and logistic regression analyses were used to assess the risk-adjusted association between hospital volume and outcomes. Results: In risk-adjusted analyses, patients operated on at low-volume hospitals were 3.04 (p = 0.03) times more likely to die after BCT compared with patients operated on at high-volume hospitals. Similarly, low-volume hospitals had a significantly higher likelihood of postoperative complications (odds ratio [OR] = 1.73, p = 0.01 for BCT; OR = 1.44, p < 0.001 for BAT) compared with high-volume hospitals. Compared with low-volume hospitals, length of hospital stay was significantly shorter and nonroutine patient discharge significantly lower for high-volume providers for both BCT and BAT (all p < 0.001). Patients were also significantly less likely to undergo BCT if operated on in a low- or intermediate-volume hospital compared with a high-volume provider (p < 0.001). Conclusions: High-volume hospitals had significantly lower nonroutine patient discharge, postoperative morbidity and mortality, shorter length of hospital stay, and higher likelihood of performing BCT. Referral of patients with localized breast cancer to high-volume hospitals may be justified.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Association of Community Economic Distress and Breast and Colorectal Cancer Screening,Incidence, and Mortality Rates Among US Counties

Introduction

Not all Americans may benefit equally from current improvements in breast and colorectal cancer screening and mortality rates.

Methods

We performed a cross-sectional retrospective review of county-level screening, incidence, and mortality rates for breast and colon cancer utilizing three publicly available data sources from the Centers for Disease Control and Prevention (CDC), and their association with the Distressed Communities Index (DCI), a measure of local economic prosperity across communities.

Results

After controlling for other factors, DCI was associated with county-level screening, incidence, and death rates per 100,000 for breast and colorectal cancer. There was an absolute increase of 0.77 (95% confidence interval [CI] 0.67–0.85, p < 0.001) in the proportion of women aged 40 years or older who had a screening mammogram for every 10-point decrease in DCI, which in turn correlated with an increase in the age-adjusted incidence by 1.68 per 100,000 (95% CI 1.37–2.00, p < 0.001). While the age-adjusted death rate for breast cancer was highest in the most distressed communities, the overall incidence of age-adjusted death decreased by 0.28 per 100,000 (95% CI ?0.37 to ?0.19, p < 0.001) with every 10-point decrease in DCI. For colorectal cancer, every 10-point decrease in DCI was similarly associated with an absolute 0.60 (95% CI 0.52–0.69, p < 0.001) increase in the proportion of individuals who had screening endoscopy. Increased colorectal screening in low-DCI counties was associated with a lower age-adjusted incidence rate (?0.80 per 100,000; 95% CI ?0.94 to ?0.65) and age-adjusted death rate (?0.55 per 100,000; 95% CI ?0.62 to ?0.49) of colorectal cancer per every 10-point decrease in DCI (p < 0.001).

Conclusion

The association of county-level socioeconomic and healthcare factors with breast and colorectal cancer outcomes was notable, with level of community distress impacting cancer screening, incidence, and mortality rates.

     

Use of B-Type Natriuretic Peptide to Predict Blood Pressure Improvement after Percutaneous Revascularisation for Renal Artery Stenosis

ObjectivesThe purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA).MethodsIn 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA.ResultsBP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml^?1 (interquartile range (IQR) 35–250) and decreased significantly within 1 day of PTRA to 62 pg ml^?1 (IQR 24–182) (p < 0.001), remaining at 75 pg ml^?1 (IQR 31–190) at 6 months. The area under the receiver operating curve for pre-intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46–0.67). Pre-intervention BNP >50 pg ml^?1 was seen in 79% of patients with BP improvement compared with 56% in patients without improvement (p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml^?1 was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2–13.2).ConclusionsBNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml^?1 may be helpful to identify patients in whom PTRA will improve BP.     

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients with chronic kidney disease

BackgroundChronic kidney disease (CKD) can increase serum carcinoembryonic antigen (CEA) levels. We thus aimed to evaluate the impact of CKD on CEA prognostic accuracy in colorectal cancer.MethodsAltogether, 429 patients who underwent curative resection for stages I–III colorectal adenocarcinoma were grouped according to postoperative CEA levels and history of CKD.ResultsThree-year disease-free survival (DFS) was higher in patients with normal postoperative CEA (group A, 83.4%) than in those with elevated postoperative CEA (group B, 64.3%) (p < 0.001). CKD patients had higher postoperative CEA levels than non-CKD patients (odds ratio 3.27, 95% confidence interval 1.78–5.99, p < 0.001). In multivariable analysis, postoperative CEA level was an independent prognostic factor for DFS in non-CKD, but not CKD, patients.ConclusionsCKD can increase postoperative CEA levels in colorectal cancer patients. Elevated postoperative CEA levels were associated with shorter DFS in non-CKD, but not CKD, patients.     

Decisional conflict in breast cancer patients considering immediate breast reconstruction

BackgroundBreast cancer (BC) patients who are treated with mastectomy are frequently offered immediate breast reconstruction. This study aimed to assess decisional conflict in patients considering immediate breast reconstruction, and to identify factors associated with clinically significant decisional conflict (CSDC).MethodsBaseline data of a multicenter randomized controlled trial evaluating the impact of an online decision aid for BC patients considering immediate breast reconstruction after mastectomy were analyzed. Participants completed questionnaires assessing sociodemographic and clinical characteristics, decisional conflict and other patient-reported outcomes related to decision-making such as breast reconstruction preference, knowledge, information resources used, preferred involvement in decision-making, information coping style, and anxiety. Multivariable logistic regression analysis was performed to identify factors associated with CSDC (score > 37.5 on decisional conflict).ResultsOf the 250 participants, 68% experienced CSDC. Patients with a slight preference for breast reconstruction (odds ratio (OR) = 6.19, p < .01), with no preference for or against breast reconstruction (OR = 11.84, p < .01), and with a strong preference for no breast reconstruction (OR = 5.20, p < .05) were more likely to experience CSDC than patients with a strong preference for breast reconstruction. Furthermore, patients with more anxiety were more likely to experience CSDC (OR = 1.03, p = .01).ConclusionA majority of BC patients who consider immediate breast reconstruction after mastectomy experience clinically significant decisional conflict. The findings emphasize the need for decision support, especially for patients who do not have a strong preference for breast reconstruction.     

Primary Breast Neuroendocrine Tumors: An Analysis of the National Cancer Database

Background

Primary breast neuroendocrine tumors (BNETs) represent < 1% of breast cancers. Diagnosing BNETs can be challenging, and a limited amount of cohort data currently exists in literature. We aimed to describe primary BNET characteristics, treatment modalities, and survival outcomes through the National Cancer Database (NCDB).

Methods

A retrospective cohort analysis was performed using the NCDB from 2004 to 2017. BNET cases were compared with patients with invasive ductal carcinoma (IDC). A matched IDC cohort was created by matching patient age, race, and disease stage. Kaplan–Meier analysis was performed, and hazard ratios (HR) were calculated through the bootstrap sampling method.

Results

A total of 1389 BNET and 1,967,401 IDC cases were identified. When compared with IDC patients, BNET patients were older, had more comorbidities, and were more often male (p < 0.01). BNETs were larger, higher grade, and more frequently hormone receptor negative (p < 0.01). While BNET patients were treated with surgery and radiotherapy (p < 0.01) less often compared with IDC patients, they presented at later disease stage (p < 0.001) and received systemic treatment more frequently (53.5% vs. 40%, p < 0.01). Patients with BNET had increased mortality compared with the matched IDC cohort: stage 1 HR 1.8, stage 2 HR 2.0, stage 3 HR 1.8, and stage 4 HR 1.5 (p < 0.001 for all).

Conclusion

Patients with BNET tend to present at higher clinical stages, are more frequently hormone receptor negative, and have inferior overall survival compared with patients with IDC. Further treatment strategies and studies are needed to elucidate optimal therapies to maximize patient outcomes.

     

Disparities in Receipt of Lymph Node Biopsy Among Early-Stage Female Breast Cancer Patients

Accurate staging of early breast cancer requires pathological assessment of axillary lymph node involvement. We evaluated the proportion of women receiving surgery for early-stage breast cancer who do not receive any lymph node biopsy (LNB) and factors associated with not receiving LNB. Patients receiving surgery for early-stage breast cancer (T1a/T1b/T1c/T2N0) during the period 2003–2005 were selected from the National Cancer Database. Patient sociodemographic, clinical, health insurance, and facility information was collected. Logistic regression was used to assess factors predictive of not receiving LNB. The number of women meeting study inclusion criteria was 184,050, 11% of whom did not receive any LNB. Compared with White patients, Black patients had greater likelihood [odds ratio (OR) 1.10, p < 0.001] of receiving no LNB; there were no significant differences for Hispanic or other non-White patients. Individuals who were uninsured (OR 1.24, p < 0.0005) or covered by Medicare at age <65 years (OR 1.29, p < 0.0001) had greater likelihoods of no LNB compared with those with private insurance. Medicaid patients and Medicare patients ≥65 years were not significantly different from private insurance patients. Compared with the youngest quartile of patients (age ≤51 years), patients in the oldest quartile (age ≥73 years) were more than three times as likely (OR 3.30, p < 0.0001) not to receive any LNB. We conclude that, while guidelines indicate that LNB may be considered optional in certain patient groups, it remains a key component in determining stage, and thereby prognosis and appropriate treatment options. These results indicate that significant disparities exist in sampling of axillary lymph nodes among women with early-stage breast cancer. A portion of this work was performed while Michael Halpern and Nicole Marlow were members of the Dept. of Health Services Research, American Cancer Society, Atlanta GA.     

Effect of postmastectomy radiotherapy on pT1-2N1 breast cancer patients with different molecular subtypes

ObjectiveTo clarify the effect of postmastectomy radiotherapy (PMRT) on pT_1-2N₁ breast cancer patients with different molecular subtypes.MethodsWe retrospectively analyzed the data of 5442 patients with pT_1-2N₁ breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR).ResultsWith a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p < 0.001). PMRT was independently associated with reduced LRR after adjustments for confounders (p < 0.001). After grouping the patients according to the molecular subtype of cancer and conducting PSM, we found that the 5-year LRR rates among patients treated with and without PMRT (in that order) were as follows: luminal HER2-negative cancer, 1.9% and 6.5% (p < 0.001); luminal HER2-positive cancer, 3.8% and 13.7% (p = 0.041); HER2-overexpressing cancer, 10.2% and 15.5% (p = 0.236); and triple-negative cancer, 4.6% and 15.9% (p = 0.002). Among patients with HER2-overexpressing and triple-negative cancers, the LRR hazard rate displayed a dominant early peak, and was extremely low after 5 years. However, patients with luminal cancer continued to have a long-lasting high annual LRR hazard rate during follow-up.ConclusionPMRT significantly reduced the LRR risk in patients with pT_1-2N₁ luminal and triple-negative breast cancers, but had no effect on the LRR risk in patients with HER2-overexpressing cancer. Patients with different molecular subtypes displayed different annual LRR patterns, and the late recurrence of the luminal subtype suggests the necessity of long-term follow-up to evaluate the efficacy of PMRT.     

Fatigue,anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls

BackgroundWomen with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls.MethodWomen with breast cancer (N = 196) filled in 5 questionnaires 1–2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue – Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires.ResultsThe patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p ≤ 0.001).ConclusionMost women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints.     

Lysozyme expression by breast carcinomas, correlation with clinicopathologic parameters, and prognostic significance

Background:Here we evaluate the expression and prognostic value of lysozyme, a milk protein that is also synthesized by a significant percentage of breast carcinomas, in women with breast cancer.Methods:Lysozyme expression was examined by immunohistochemical methods in a series of 177 breast cancer tissue sections. Staining was quantified by using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The prognostic value of lysozyme was retrospectively evaluated by multivariate analysis that took into account conventional prognostic factors.Results:A total of 126 of 177 carcinomas (69.4%) stained positive for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Lysozyme values were higher in well-differentiated and moderately differentiated tumors than in poorly differentiated tumors (P < .05). Similarly, lysozyme levels were higher in small and node-negative tumors than in large and node-positive tumors (P < .05). Moreover, results indicated that low lysozyme content predicted shorter relapse-free survival and overall survival (P < .005). Separate Cox multivariate analysis in subgroups of patients as defined by node status showed that lysozyme expression was an independent prognostic factor able to predict both relapse-free survival and overall survival in node-negative patients (P < .05).Conclusions:Tumoral expression of lysozyme is associated with lesions of favorable evolution in breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer.