Stage I Breast Cancer in the Modern Era: A Retrospective Cohort Study of 328 Patients Diagnosed from 2002 to 2006 with a 14- year Median Follow-Up.

INTRODUCTION: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. METHODS: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS). The influence of tumor size, grade, and subtype on the outcomes was analyzed. RESULTS: Most patients were treated by lumpectomy, sentinel node biopsy and adjuvant endocrine therapy and most (82%) were of subtype luminal-A. Adjuvant chemotherapy was administered to 25.6 % of our cohort. Only 24 patients underwent gene expression testing, which was introduced toward the end of the study period. Mean IDFS was 14.64 years, with a 15-year IDFS of 75.6%. Mean OS was 15.28 years with a 15-year OS of 74.9%. In a Cox multivariate analysis, no clinical or pathologic variable impacted on OS and only tumor size (< 1 centimeter (cm) vs 1-2 cm), impacted significantly on IDFS. During follow-up, 20.1% of the cohort developed second primary cancers, including BC. The median time to diagnosis of a second BC was 6.49 years. CONCLUSION: The study results emphasize the importance of long-term follow-up and screening for subsequent malignancies of patients with stage I BC and support the need for using prognostic and predictive indicators beyond the routine clinicopathological characteristics in luminal-A patients.

Neoadjuvant therapy with doxorubicin-cyclophosphamide followed by weekly paclitaxel in early breast cancer: a retrospective analysis of 200 consecutive patients treated in a single center with a median follow-up of 9.5 years.

PURPOSE: We analyzed outcomes of doxorubicin-cyclophosphamide (AC) followed by weekly paclitaxel as neoadjuvant chemotherapy (NAC) for breast cancer (BC), in an everyday practice with long-term follow-up of patients. METHODS: All patients (n = 200) who received the AC-paclitaxel combination as NAC for BC at the Soroka University Medical Center from 2003 to 2012 were included in this retrospective cohort study. AC was administered on an every 3-week schedule (standard dose) until May, 2007 (n = 99); and subsequently every 2-week dose dense (dd) (n = 101). Clinical pathologic features, treatment course, and outcome information were recorded. Complete pathologic response (pCR) was analyzed according to BC subtype, dose regimen, and stage. RESULTS: Median age was 49 years; 55.5% and 44.5% of patients were clinically stage 2 and 3, respectively. Standard dose patients had more T3 tumors. Subtypes were human epidermal growth factor receptor-2 (HER2)-positive 32.5% (of whom 82% received trastuzumab), hormone receptor-positive/HER2-negative 53%, and triple negative 14.5%. Breast-conserving surgery (BCS) was performed in 48.5% of patients; only 9.5% were deemed suitable for BCS prior to NAC. Toxicity was acceptable. The overall pCR rate was 26.0% and was significantly higher in the dd group and HER2-positive patients. With a median follow-up of 9.51 years median event-free survival (EFS) and overall survival (OS) are 10.85 years and 12.61 years, respectively. Patients achieving pCR had significantly longer EFS and OS. CONCLUSION: NAC for BC with AC-paclitaxel can be safely administered in the "real-world' setting with high efficacy. Current efforts are aimed at increasing rates of pCR and identifying patients who may benefit from additional therapy or conversely, de-escalated treatment.

Post Mastectomy Radiation for Stage II Breast Cancer Patients with T1/T2 Lesions.

OBJECTIVE: Post mastectomy radiation (PMR) is usually recommended for T3 or N2 breast cancer (BC). The role of PMR for stage II BC with T1/T2 lesions remains controversial. The aim of this study was to assess the role of PMR in this subgroup of patients. MATERIALS AND METHODS: A retrospective analysis of a prospectively collected database of all stage II BC patients treated with mastectomy at our institution between the years 2005-2008 was performed. Demographics, disease-free survival rates were compared between the patients receiving radiation vs. those who were not irradiated. RESULTS: Eighty-two patients underwent mastectomies for stage II disease with a T1/T2 lesion. Twenty-two of those (27%) received PMR. Loco regional recurrence (LRR) occurred only in the non -irradiated (NR) group. A Kaplan Meier analysis of time to LRR in the NR group was performed. Mean time to local failure was 78.9 months, 6% at 3 years and 13% at 5 years. The time to LRR was significantly lower in the estrogen receptor (ER) negative group compared to the ER positive group (64 vs. 82 months, p=0.029). LRR free rate at 5 years was 100% in low grade tumors vs. 53% in high grade tumors, (p=0.001). In a Cox regression multivariate analysis none of those factors maintained significance. CONCLUSION: ER negative status, high grade and node negativity were associated with LRR. A prospective trial randomizing stage II BC patients with T1/T2 lesions, negative hormone receptors and high-grade tumors to PMR following mastectomy arm vs. no radiation arm is recommended.

Early non-invasive detection of breast cancer using exhaled breath and urine analysis.

The main focus of this pilot study is to develop a statistical approach that is suitable to model data obtained by different detection methods. The methods used in this study examine the possibility to detect early breast cancer (BC) by exhaled breath and urine samples analysis. Exhaled breath samples were collected from 48 breast cancer patients and 45 healthy women that served as a control group. Urine samples were collected from 37 patients who were diagnosed with breast cancer based on physical or mammography tests prior to any surgery, and from 36 healthy women. Two commercial electronic noses (ENs) were used for the exhaled breath analysis. Urine samples were analyzed using Gas-Chromatography Mass-Spectrometry (GC-MS). Statistical analysis of results is based on an artificial neural network (ANN) obtained following feature extraction and feature selection processes. The model obtained allows classification of breast cancer patients with an accuracy of 95.2% ±â€¯7.7% using data of one EN, and an accuracy of 85% for the other EN and for urine samples. The developed statistical analysis method enables accurate classification of patients as healthy or with BC based on simple non-invasive exhaled breath and a urine sample analysis. This study demonstrates that available commercial ENs can be used, provided that the data analysis is carried out using an appropriate scheme.

A review of clinical aspects of breast cancer.

Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer related death in women. The ability to identify and diagnose breast cancer has improved markedly. Treatment decisions which were based in the past predominantly on the anatomic extent of the disease are shifting to the underlying biological mechanisms. Gene array technology has led to the recognition that breast cancer is a heterogeneous disease composed of different biological subtypes, and genetic profiling enables response to chemotherapy to be predicted. Breast conservation became an established standard of care and the oncoplastic approach enables wide excisions without compromising the natural shape of the breast. Sentinel lymph node biopsy has replaced axillary dissection as the standard procedure to stage the axilla and spared many patients the excess morbidity of axillary dissection. Targeted therapy to the oestrogen receptor plays a major role in systemic therapy; pathways responsible for endocrine resistance have been targeted as well. Biological therapy has been developed to target HER2 receptor and combination of antibody drug conjugates linked cytotoxic therapy to HER2 antibodies. Meaningful improvements in survival resulted from the new effective systemic agents and patients with metastasis are likely to have a longer survival.

Persistence of pathogens despite clinical improvement in antibiotic-treated acute otitis media is associated with clinical and bacteriologic relapse.

BACKGROUND: Pathogen eradication in patients with acute otitis media (AOM) is associated with a reduced risk of clinical failures, but most children in whom middle ear fluid (MEF) culture remains positive show clinical improvement or clinical cure. We investigated the relationship between MEF culture-positivity during treatment in patients with clinical improvement/cure, and the occurrence of subsequent AOM. METHODS: A total of 673 patients with culture-positive MEF were enrolled in double-tympanocentesis studies and followed for 3 weeks after completion of treatment. RESULTS: On day 4-6, 189/673 (28%) patients had culture-positive MEFs. Patients with clinical improvement/cure on day 11-14 (end of treatment) despite having culture-positive MEF on day 4-6 more often had recurrent AOM episodes (53/151, 35%) than those with culture-negative MEF (114/476, 24%; P = 0.007). 41/53 (77%) culture-positive patients with clinical improvement/cure on day 11-14 underwent tympanocentesis when AOM recurred and 29/41 (71%) were culture-positive. Pulsed field gel electrophoresis identity between pathogens at recurrence and those persisting on day 4-6 was found in 19/29 (66%) compared with 31/86 (36%) of the evaluable patients with recurrence and culture-negative MEF on day 4-6 (P = 0.005). CONCLUSIONS: (1) Failure to eradicate MEF pathogens during antibiotic treatment is associated with clinical recurrences, even in patients showing clinical improvement/cure at end of treatment; (2) these recurrences are mostly caused by pathogens initially present in MEF and persisting during treatment.

Evaluation of compensatory sweating after bilateral thoracoscopic sympathectomy for palmar hyperhidrosis.

The study is a retrospective review of 60 patients undergoing bilateral T2-T3 thoracoscopic sympathectomy for palmar hyperhidrosis in our department between 1997 and 2003. The study was based on a telephone questionnaire and medical chart review. Forty patients (67%) replied to the questionnaire and were included in the study. Postoperative complications, therapeutic results, patient satisfaction, and the severity of compensatory sweating (CS) were assessed. In all patients both palms were dry at the end of surgery. Postoperative complications included permanent unilateral Horner syndrome, wound infection, and residual pneumothorax resolving after thoracal drainage, in one patient each. CS with different severity occurred in 35 patients (87.5%). Six patients (15%) regretted undergoing the operation due to the extent and severity of the CS seriously affecting their quality of life. Thoracoscopic sympathectomy is a simple procedure with a high success rate. However, CS is a serious complication and a significant number of patients may regret undergoing the operation; a careful selection of patients and comprehensive explanation are advisable.

Nasopharyngeal carriage of Streptococcus pneumoniae at the completion of successful antibiotic treatment of acute otitis media predisposes to early clinical recurrence.

OBJECTIVE: We sought to investigate the role of Streptococcus pneumoniae (SP) nasopharyngeal (NP) colonization after successful antibiotic treatment (Rx) of acute otitis media (AOM) in recurrent AOM (RAOM). PATIENTS AND METHODS: NP cultures were obtained from 494 (93%) of 530 patients at the end of antibiotic treatment (EOT). RESULTS: At enrollment, middle ear fluid (MEF) cultures in 418 (79%) of 530 patients were positive for pathogens. At EOT, NP cultures in 208 (42%) of 494 patients were positive for SP. RAOM was found in 130 (26%) of 494 patients: 66 (32%) of 208 with SP-positive NP and 64 of 286 (22%) without SP-positive NP at EOT (P=.026). MEF was positive for SP during RAOM in 34 (61%) of 56 patients with SP-positive NP and 17 (36%) of 47 patients without SP-positive NP at EOT (P=.022). The same serotype was identified in 24 (80%) of 30 SP pairs; complete identity was found between isolates in 22 (96%) of 23 SP pairs. CONCLUSIONS: Early RAOM was more commonly caused by SP if the organism was present in NP at EOT during the initial AOM episode. Most SP-RAOM episodes were caused by SP isolates present in NP at EOT during the previous AOM episode.