IIB Breast Cancer Research Articles

Neoadjuvant chemotherapy and pathological complete response in hormone-positive HER2-negative breast cancer: influence of progesterone receptor expression, tumor grade and Ki-67

Aim. To study the role of progesterone receptor expression, tumor grade and Ki-67 level as possible predictors of pathological complete response (pCR) to neoadjuvant chemotherapy in patients with stage IIA–IIB (cT1–2N1, cT2–3N0M0) breast cancer of hormone-positive HER2-negative subtype.Materials and methods. We retrospectively analysed the efficacy of neoadjuvant chemotherapy (4AC+12P/4T) in 100 patients with cancer stages IIA–IIB (cT1–2N1, cT2–3N0M0) of hormone-positive HER2-negative subtype treated at the P.A. Hertsen Moscow Oncology Research Institute from 2013 to 2022. The pathological response to neoadjuvant chemotherapy depending on the level of progesterone receptor expression, tumour grade (G) and tumour proliferation index (Ki-67) were evaluated.Results. Pathological complete response was achieved in 12 of 100 patients. The progesterone receptor expression ≤3 Allred pCR scores were found in 16.1 % (5/31) of patients, whereas with progesterone receptor >3 scores in 10.1 % (7/69) (odds ratio 1.703; 95 % confidence interval (CI) 0.495–5.860; p = 0.507). Patients with high tumour grade (G3) achieved pCR in 12.1 % (4/33) cases and with G2 – in 11.9 % (8/67) (odds ratio 1.017; 95 % CI 0.283–3.658; p = 1.000). With the Ki-67 levels ≥50 % pCR was achieved in 14.6 % (7/48) cases compared to 9.6 % (5/52) with Ki-67 levels <50 %(odds ratio 1.605; 95 % CI 0.473–5.445; p = 0.544). The Ki-67 threshold for achieving pCR was 70 % (area under the ROC curve 0.663 ± 0.090; 95 % CI 0.486–0.840; p = 0.068) and for progesterone receptors was 3 points (area under the ROC curve 0.625 ± 0.080; 95 % CI 0.467–0.782; p = 0.156).Conclusion. This analysis highlights the importance of considering all clinical and morphological characteristics of the tumour when planning the scope of treatment for hormone-positive HER2-negative breast cancer. The results obtained may serve as a basis for a more personalised therapeutic approach.

The effect of radiotherapy on patients with pathological stage IIB breast cancer after breast-conserving surgery or mastectomy: A cohort study.

Breast cancer is one of the most common cancers in women, and treatment options include surgery, systemic therapies, and radiotherapy (RT). While postoperative RT plays an important role in reducing local recurrence rates and improving survival outcomes, its exact impact on patients with pathological stage IIB breast cancers remains unidentified. In this retrospective cohort study, patients with newly diagnosed pathological stage IIB breast cancer who underwent surgery and postoperative RT were included. The data were collected from medical records, and survival outcomes were assessed using the Kaplan-Meier method, log-rank tests, and Cox regression models. In total, 350 patients participated in this study. Overall survival, locoregional recurrence-free survival, event-free survival, and distant metastasis-free survival rates did not significantly differ between those who received RT and those who did not. Multivariate analyses revealed that patients who received anthracycline or taxane chemotherapy had better survival outcomes. Our findings demonstrated that postoperative RT had no significant effect on overall survival, locoregional recurrence, event-free survival, or distant metastasis rates in patients with pathological stage IIB breast cancer. However, anthracycline- and taxane-based chemotherapies were associated with improved outcomes. These findings demonstrated the complexities of treating such patient populations with multimodal therapies. Further research is needed to ensure optimal postoperative RT in patients with pathological stage IIB breast cancer. Clinicians must consider individual patient characteristics and incorporate comprehensive treatment approaches to ensure successful outcomes in this population.

When Hormones are Being Difficult: A Rare Case and the Literature Review of Pembrolizumab-Induced Polyendocrinopathy.

Immune Checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab, and ipilimumab are monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA4) or program death (PD)1 and its ligand PDL1. Agents targeting PD1, such as pembrolizumab, have shown widespread efficacy in the past and are also associated with a wide range of immune-related adverse events (irAEs), including endocrine toxicities. A 31-year-old female with a medical history significant for Stage IIb Breast cancer on chemo and immunotherapy (pembrolizumab) presented with nausea, vomiting, and generalized abdominal pain. Laboratory studies showed a blood glucose level of 356 mg/dl, elevated Anion gap 18 meq/L, beta-hydroxybutyrate 46 mg/d, and low C-peptide levels <0.10 ng/ml. The patient was treated for Diabetic Ketoacidosis (DKA). Further testing revealed high Thyroid Stimulating Hormone (TSH) levels along with elevated thyroid peroxidase levels of 38 IU/L. After discharge from the hospital on insulin and levothyroxine therapy, the patient reported increasing fatigue and further testing revealed low cortisol levels <0.5 mcg/dl with elevated ACTH consistent with primary adrenal insufficiency. The patient was started on hydrocortisone therapy with improvement in symptoms. Endocrine toxicities are not uncommon in patients receiving pembrolizumab, but polyendocrinopathy in a relatively rare side effect of pembrolizumab. Only a few cases of pembrolizumab-induced polyendocrinopathy have been reported so far which we have mentioned in this article. While patients are on immunotherapy, close monitoring for clinical signs & symptoms can lead to an early diagnosis, substantially improving morbidity and mortality.

Body image perception among breast cancer patients after mastectomy: A phenomenology study

Background: Breast cancer is the most common type of cancer among all cancers. Most breast cancer treatments involve surgery, which leads to changes in body shape. These changes can have an impact on body image after mastectomy, affecting the patients’ quality of life. Objective: This study aimed to explore the perception of body image of breast cancer patient after mastectomy. Methods: A qualitative phenomenological approach was employed in this study. A total of 15 post-mastectomy clients were recruited through purposive sampling technique. Data collection involved semi-structured interviews, which were recorded. The data were analyzed using the Van Mannen approach with the assistance of NVivo 12 Plus software. Results: The majority of the participants were in the elderly phase, with an average education level of junior high school. Most had a history of stage IIB breast cancer and, on average, had undergone mastectomy three years ago. This study identified the theme of body image, which consisted of four categories and eleven sub-categories. Conclusions: The description of body image in post-mastectomy clients includes beliefs, thoughts, feelings, and behaviors. This response is influenced by the belief in the importance of breasts, optimism regarding achieving one’s ideal self, thoughts about changes in the body, acceptance of oneself and those around us, enthusiasm for healing and comfort, and social roles.

The Radiologist at the Center of Breast Conservation in the Management of Breast Cancer: A Case-Based Narrative Review of the Literature

The management of breast cancer involves a multidisciplinary team approach involving the surgeon, radiologist, pathologist, radiotherapist, and clinical oncologist. Radiology in the management of breast cancer patients allows for lesion detection and characterization, confirmation of diagnosis with image-guided biopsy, post-biopsy placement of clip marker, confirmation of patients’ eligibility for breast conservation surgery, image-guided localization, staging, evaluation of response to therapy before surgery, and follow-up after treatment for breast cancer. This narrative review is based on a case of a 35-year-old woman offered breast-conserving therapy for stage IIB breast cancer in a tertiary hospital in Southwest Nigeria. This case-based review highlights the radiologist’s vital role in breast conservation in the management of breast cancer, elaborating on the radiological management of this patient.

Is there an Association of Glycosylated Haemoglobin A1c and Anthropometric Measurements in Premenopausal and Postmenopausal Breast Cancer Patients?

Background: Breast cancer is the commonest malignancy among women globally. It is a leading cause of cancer death in less developed countries and the second leading cause of cancer death in developed countries. Diabetes and breast cancer are two conditions that frequently coexist, and menopause may be a metabolic watershed. The purpose of this study is to examine the relationship between glycosylated haemoglobin (HbA1c) and anthropometric measurements in premenopausal and postmenopausal breast cancer patients Methods: 100 patients diagnosed with breast cancer between December 2020 to November 2022 were evaluated and their HbA1c levels were correlated with anthropometric measurements and tumour characteristics Results: In our study mean age of the patients was 47.75 ±11.77 SD years. In patients with normal HbA1c 64% patients were pre-menopausal. In Pre-diabetic HbA1c group 70% were post-menopausal and in diabetic HbA1c group 93% were postmenopausal. Mean waist circumference was 84.56 ± 6.64 SD cms; more in pre-diabetic and diabetic patients; (p value 0.000). Most of the patients (71%) had waist to hip ratio ≥0.85 (p value 0.349). Pre-diabetic and diabetic patients were overweight (p value 0.000). 6 patients were known cases of type II diabetes mellitus and were on insulin/OHAs. T3 tumours were more common in both premenopausal and postmenopausal patients followed by T4 tumours. Stage IIB breast cancer was present in 39% of premenopausal and stage IIIA was seen in 30% of the postmenopausal patients. Grade II disease was more common in both premenopausal and postmenopausal (p value 0.858). Invasive ductal carcinoma-No special type (IDC-NST) was seen in 77% of the patients (p value 0.156). Estrogen Receptor (ER) positivity was seen in 42% of premenopausal and 33% of postmenopausal patients, negative Progesterone Receptor (PR) seen in 86% in premenopausal and 89% in postmenopausal patients and positive Her2 neu receptor was observed in 30% in premenopausal and 56% in postmenopausal patients. Conclusion: Our study demonstrated that a considerable proportion of breast cancer patients were prediabetic. Glycaemic status and HbA1c were clearly associated with measures of visceral obesity in carcinoma of breast patients. Postmenopausal patients had higher levels of HbA1c compared to premenopausal cases. However; clinicopathological and tumour characteristics in our study didn’t demonstrate any significant correlation with glycaemic status and need more research and randomized controlled trials. Collectively, findings from our study particularly emphasize the need to control hyperglycemia and identify vulnerable groups of breast cancer patients who might benefit from interventions to improve glycaemic control.

The possibility of performing organ-sparing surgical treatment in patients with Stage IIB, IIIA, or IIIC breast cancer after neoadjuvant polychemotherapy

<h3></h3> Несмотря на широкое распространение органосохраняющих операций (ОСО) у больных ранним раком молочной железы (РМЖ), их выполнение при РМЖ IIB, IIIA, IIIC стадий в настоящее время остается дискутабельным. <h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Изучение возможности проведения ОСО у больных местно-распространенным раком молочной железы с учетом эффективности неоадъювантной полихимиотерапии (НАПХТ). <h3>МАТЕРИАЛ И МЕТОДЫ</h3> С 2013 по 2020 г. проанализирована медицинская документация 55 пациенток с РМЖ IIB, IIIA, IIIC стадий, которым на втором этапе комплексного лечения произведены ОСО после НАПХТ в отделении онкологии и реконструктивно-пластической хирургии молочной железы и кожи МНИОИ им. П.А. Герцена. Распределение по стадиям было следующим: IIB — 67,3%, IIIA — 9,3%, IIIC — 26,3% пациенток. <h3>РЕЗУЛЬТАТЫ</h3> Из 100 больных РМЖ cT1-3N0-3M0 кандидатами на выполнение радикальной мастэктомии были 55 пациенток до начала НАПХТ (IIB, IIIA, IIIC стадии РМЖ). Однако на фоне проведенной предоперационной полихимиотерапии клинически отмечена положительная динамика в виде частичной (32/58,2%) и полной (12/21,8%) резорбции опухолевого узла и пораженных регионарных лимфатических узлов, в связи с чем у данной группы больных стало возможно выполнение ОСО. Стандартный подход, подразумевающий отсутствие опухолевых клеток в краях резекции, продемонстрировал высокий процент 3- и 5-летней безрецидивной выживаемости, частота развития рецидива в течение 7 лет наблюдения составила 1,8%. Безрецидивная выживаемость в течение 3 лет была 98,5%, 5 лет — 98,5%, 3-летняя общая выживаемость составила 89,6%, 5-летняя — 84,9%. <h3>ЗАКЛЮЧЕНИЕ</h3> Таким образом, на основании проведенного исследования установлено, что органосохраняющие операции после НАПХТ у больных РМЖ IIB, IIIA, IIIC стадий безопасны с онкологической точки зрения при достижении положительной динамики на фоне лечения.

Abstract P6-11-16: Survey on attitude towards treatment recommendations for elderly patients with breast cancer

Abstract Background: With the rapid aging of the society, breast cancer in elderly people is also increasing. Although it is important to avoid unnecessary toxicity to maintain the quality of life of elderly patients, it is suggested that they are undertreated compared to younger counterparts which leads to poorer outcomes. The objective of this study was to assess the practice of the clinical care for elderly breast cancer patients aged 75 or over, and to explore the factors associated with physicians’ attitude regarding treatment recommendations towards elderly breast cancer patients in Japan. Methods: We conducted an online survey towards 1690 Breast Care Specialists belonging to the Japanese Breast Cancer Society. The respondents were asked to complete a questionnaire including (1) sociodemographic background, (2) hypothetical case scenarios in patients with Stage IIB breast cancer, (3) clinical experience of elderly breast cancer patients, (4) Good Death Inventory (GDI), a measure for evaluating good death from the bereaved family member's perspective and (5) belief regarding cancer treatment for elderly breast cancer patients. We used descriptive statistics to summarize respondents' sociodemographic data. Chi-square tests were used to evaluate differences in proportion. Differences in GDI scores were estimated using Mann-Whitney tests. Statistical analyses were performed using SPSS software. Results: 508 (30%) physicians responded to the survey. 353 (69.4%) were male. 464 (91.3%) were breast surgeons and 43 (8.4%) were others, including medical oncology, radiology and general surgery. 46 (9%), 115 (22.6%), 284 (55.9%) and 47 (9.3%) belonged to cancer centers, university hospitals, general hospitals and clinics, respectively. 136 (26.8%) of the physicians responded that they have a specialized department or a team which serve for elderly patients in their institutions, whereas 369 (72.6%) answered there was no such support. In questions based on hypothetical case scenarios, significantly more physicians responded that they would not recommend chemotherapy in a 78 year-old with luminal-type breast cancer, good performance status (PS) and no complications compared to a 55 year-old with the same clinical status (p&amp;lt;0.001). Physicians who would recommend chemotherapy significantly decreased in a clinical scenario of a 78 year-old with the same clinical stage and subtype but with a lower PS and some complications (p&amp;lt;0.001). More physicians recommended chemotherapy in a 78 year-old with HER2 type tumor compared to a patient with luminal type tumor when the PS and complication status were the same (p&amp;lt;0.001). The respondents’ GDI Scores were not related to the treatment recommendations in any clinical scenario. Physicians who treated larger number of outpatients per day and those who had lower proportion of elderly patients in the clinic tended not to recommend chemotherapy for elderly patients with poorer PS and serious complications. Those who believed that “it is a doctor’s responsibility not to pursue aggressive chemotherapy in elderly patients” tended not to recommend chemotherapy in a 78-year-old patient with luminal type breast cancer with good PS and without complication. Conclusions: The attitude towards treatment recommendation on adjuvant chemotherapy in elderly breast cancer patients were related to performance status, complications and subtype of the tumor. Physicians’ experience and belief may also affect their attitude. Citation Format: Kanako Nakayama, Chikako Shimizu, Keiko Iino, Shigeaki Watanuki, Masataka Sawaki. Survey on attitude towards treatment recommendations for elderly patients with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-16.

Role of gamma probe-assisted intraoperative sentinel lymph node evaluation in predicting axillary breast cancer metastasis after neoadjuvant chemotherapy.

Intraoperative sentinel lymph node biopsy is a universally accepted technique to identify patients who are candidates for axillary lymph node dissection during breast cancer surgery. However, there is controversy over its use in patients who underwent preoperative neoadjuvant chemotherapy. This study aimed to examine the diagnostic value of gamma probe-assisted intraoperative sentinel lymph node examination with frozen section in breast cancer patients who had undergone preoperative neoadjuvant chemotherapy. This retrospective study included 94 tumors diagnosed with stage IIA, IIB or IIIA invasive breast cancer with locoregional lymph node metastasis who underwent surgical treatment after neoadjuvant chemotherapy. Intraoperatively, axillary sentinel lymph node sampling was done using radioactive colloid and gamma probe and materials were examined with frozen section method. Patients with positive sentinel nodes underwent axillary resection. Histopathological examination of all surgical samples was done postoperatively. In 87 of 94 tumors (92.6%), a sentinel lymph node could be identified using the method. The sensitivity, specificity and accuracy of the method for predicting axillary macro metastasis were 85.7, 86.5 and 86.2%, respectively, with 5.7% false negative rate. Sentinel lymph node identification using preoperative scintigraphy and intraoperative use of gamma probe seems to be a feasible and efficient method in terms of differentiating patients that require axillary lymph node dissection during breast cancer surgery, even when they have received neoadjuvant chemotherapy. Further large prospective studies allowing subgroup analyses are warranted.

What Do Breast Cancer Survivors Expect From Exercise?

Exercise outcome expectations (OEs) (ie, what one expects to obtain or avoid by exercising) are influential to increase exercise among cancer survivors. The aim of this study was to measure the accessibility (ie, frequency one thinks about exercise resulting in an outcome) and importance (ie, one's value of the outcome) of OEs among breast cancer survivors. Stage IA to IIB breast cancer survivors who were 1 to 5 years posttreatment completed OE questionnaires. Descriptive statistics were used to examine OE accessibility and importance. The sample (n = 73) was 91.8% white, 5.4% African American, 1.4% Asian or Pacific Islander, and 1.4% other. The mean age was 58 (SD, 9.6) years. Outcome expectation importance mean was 6.1 (SD, 0.4), indicating OEs are overall "important." Accessibility mean was 4.8 (SD, 0.6), demonstrating breast cancer survivors think about exercise OEs "sometimes/50% of the time." There was a moderate (rs = 0.48) relationship between OE importance and accessibility, indicating they are related, yet distinct. Outcome expectations are generally important to breast cancer survivors. Thus, OEs may motivate increased exercise among this population. Oncology providers should encourage patients to think about OEs more often to increase exercise. Compared with traditional approaches of informing patients about exercise benefits, this may be a more comprehensive and powerful approach to motivate exercise among breast cancer survivors.

18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Breast Cancer in Men.

18F-FDG PET/CT has demonstrated substantial value in systemic staging of newly diagnosed breast cancer in women. However, it is not known whether breast cancer in male patients benefits similarly. This study assesses 18F-FDG PET/CT systemic staging in patients with newly diagnosed male breast cancer and determines detection rates for unsuspected distant metastases stratified by pre-PET/CT stage. Methods: In this Institutional Review Board-approved retrospective study, our Health Care Information System was screened for stage I-III male patients with breast cancer who underwent 18F-FDG PET/CT before systemic or radiation therapy from 2004 to 2017. Initial stage was determined by mammography, ultrasound, or surgery. 18F-FDG PET/CT was evaluated to identify unsuspected extraaxillary regional nodal and distant metastases, and a post-PET/CT stage was determined. Rates of upstaging to stage IV were determined for each initial stage. Results: During the 14-y period, 10,124 unique patients underwent 18F-FDG PET/CT for breast cancer at our institution. Of these, 106 patients were men, and 39 of these patients were imaged at initial staging and met the inclusion criteria. Median age was 62 y (range, 31-90 y), most had ductal carcinoma (95%), and most were estrogen receptor-positive (97%). In 7 of 39 patients (18%), 18F-FDG PET/CT identified previously unsuspected distant metastases, which increased patient stage to IV. This included 3 of 19 (16%) initial stage IIB patients and 4 of 12 (33%) initial stage III patients. 18F-FDG PET/CT also detected an unsuspected synchronous lymphoma in 1 patient. Conclusion:18F-FDG PET/CT revealed previously unsuspected distant metastases in 16% of male patients with pre-PET/CT stage IIB breast cancer and 33% of those with stage III breast cancer. These rates are comparable to previously published upstaging rates in female patients. 18F-FDG PET/CT demonstrates value for systemic staging of male patients with breast cancer and should be considered for use in newly diagnosed patients, particularly those with stage IIB and III disease.

Metaplastic carcinoma of the breast : Two cases

We treated two patients with a rare metaplastic carcinoma of the breast. Patient 1：A 32-year-old woman presented with a rapidly growing mass（ 7cm） in her right breast. We diagnosed cT3N0M0 Stage IIB breast cancer and performed a radical resection. The pathological diagnosis was triple-negative metaplastic carcinoma with a Ki-67 value ＞30%. Postoperative adjuvant chemotherapy and radiotherapy were performed. Patient 2：A 66-year-old postmenopausal woman presented with a left breast mass. We diagnosed cT1N0M0 Stage I breast cancer and performed a radical resection. The pathological diagnosis was triple-negative metaplastic carcinoma with a Ki-67 value ＞30%. Postoperative adjuvant chemotherapy was performed. Patients 1 and 2 have achieved relapse-free survivals of 1 year＋2 months and 10 months, respectively. Metaplastic carcinoma of the breast is a rare tumor, and its prognosis is not favorable. The only available treatment is that used for invasive ductal carcinoma；a more specific treatment has not been established. The accumulation of further similar cases and the development of a novel effective treatment are desired.

Abstract P6-08-21: Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics

Abstract Background and Aim: The five-year survival for women with stage I-II breast cancer is 93-100%. Despite standard of care treatment, a small subset of these women suffer early breast cancer-specific mortality and die within 12 months of diagnosis. This subset of women has not been previously described. The aim of this study is to characterize the incidence, demographics, and clinical characteristics of women with early stage breast cancer who suffer early breast cancer-specific mortality. Methods: Retrospective population study of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry of women diagnosed with stage I, IIA, or IIB breast cancer between 2004 and 2010. Data were filtered to histology codes 8500-8543 and 8575. Patient demographics (age, race, ethnicity) and clinical characteristics (stage, T stage, N stage, grade, ER status, PR status) of women in the early mortality subset were compared with those of women who survived &amp;gt; 12 months via the Chi-square test and the student t-test. Results: 259,380 women formed the basis of our analysis. 4,572 women (0.018%) died within 12 months of diagnosis. Compared with those who survived &amp;gt; 12 months, women who suffered early breast cancer-specific mortality were on average older (mean age 65.7 years versus 60.3 years, p&amp;lt;0.00001) and more likely to be Hispanic (14.3% versus 8.9%, p&amp;lt;0.00001) or black (11.0% versus 9.1%, p&amp;lt;0.00001). Clinical characteristics associated with early mortality included higher stage (stage IIA 34.2% versus 29.4%, stage IIB 21.8% versus 12.9%, p&amp;lt;0.00001), higher T stage (T2 40.5% versus 28.1%, T3 3.1% versus 1.6%, p&amp;lt;0.00001), higher N stage (N1 29.7% versus 23.2%, N2 0.8% versus 0.4%, N3 0.4% versus 0.1%, p&amp;lt;0.00001), higher grade (moderate 39.3% versus 42.5%, high 40.0% versus 31.5%, p&amp;lt;0.00001), higher rates of ER negativity (27.2% versus 19.0%, p&amp;lt;0.00001), and higher rates of PR negativity (38.5% versus 30.2%, p&amp;lt;0.00001). Conclusions: Breast cancer-specific mortality within 12 months of diagnosis of stage I-II breast cancer is a rare phenomenon which has not been previously characterized. There are several demographic and clinical features associated with early mortality, however further research is needed to identify specific prognostic factors that will allow identification of women at risk for early mortality at the time of diagnosis. Citation Format: Johnson HM, Wong JH, Vohra NA, Muzaffar M. Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-21.

Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1

BackgroundBreast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have characterized these cells for the biological and molecular markers, induction of MAPK pathways as well as its response to different commercially available drugs and compounds.MethodsBreast cancer tissue sections were minced and cultured in media for several weeks. KAIMRC1 cells were successfully isolated from one of the primary breast tumor tissue cultures without any enzymatic digestion. To study the growth characteristics of the cells, wound healing assay, clonogenic assay, cell proliferation assays and live cell time-lapse microscopy was performed. Karyotyping, Immunophenotyping and molecular pathway specific compound treatment was also performed. A selective breast cancer gene expression panel was used to identify genes involved in the signal transduction dysregulation and malfunction of normal biological processes during breast carcinogenesis.ResultsThese cells are ER/PR-positive and HER2-negative. The epithelial nature of these cells was confirmed by flow cytometry analysis using epithelial cell markers. They are cuboidal in shape and relatively smaller in size as compared to established cell lines, MCF-7, MDA MB-231 and the normal breast cell line, MCF-10A. In normal cell culture conditions these cells showed the capability of growing both in monolayer as well as in 3-D conformation. They showed a doubling time in vitro of approximately 24 h. They exhibit a modal karyotype of 58–63,X with abnormalities in a couple of chromosomes. KAIMRC1 cells were found to be more responsive to drug treatment in vitro in comparison to the established MDA MB-231 and MCF-7 cell lines.ConclusionsIn conclusion we have isolated and characterized a new naturally immortalized breast cell line, KAIMRC1 with a potential to play a key role in opening up novel avenues towards the understanding of breast carcinoma.

18F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer.

This study assesses 18F-FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer. In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent 18F-FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery.18F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI). A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, 18F-FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, 18F-FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9-20%). 18F-FDG-PET/CT revealed distant metastases in 14% (95%CI: 9-20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9-24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with 18F-FDG-PET/CT at the time of initial diagnosis.

Exploration of Exercise Outcome Expectations Among Breast Cancer Survivors.

Exercise is associated with decreased recurrence risk and improved survival and quality of life for breast cancer survivors. However, only an estimated 17% to 37% of survivors adhere to the American Cancer Society exercise guidelines. A critical first step to increase exercise among survivors is to understand how they believe exercise will affect them. The aim of this study is to explore common exercise outcome expectations among 20 female survivors of stage IA to IIB breast cancer who completed adjuvant treatment and an exercise intervention. A mixed-method descriptive study consisting of semistructured telephone interviews assessed exercise outcome expectations and how the experience of cancer and its treatment influenced the expected outcomes of exercise. The qualitative data were analyzed using a summative content analysis procedure; means were calculated for each item of the exercise outcome questionnaire. The qualitative and quantitative data were compared and contrasted. The sample was 70% white and 30% African American, with a mean (SD) age of 62 (8.5) years, and mean (SD) time since treatment completion of 4.2 (1.3) years. Three themes emerged from the interviews: (1) prevalence of common expectations, (2) pervasive impact of fatigue, and (3) a brighter future. Overall, findings revealed that breast cancer survivors have low levels of agreement that exercise may mitigate late and long-term cancer and treatment effects. In general, breast cancer survivors (even those who are motivated to exercise) do not hold strong beliefs that exercise will decrease late and long-term treatment effects. Clinicians can educate survivors about exercise benefits.

Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker.

Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (p<0.05). The clinical relevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2 protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2 mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery.

(18)F-FDG-PET/CT for systemic staging of newly diagnosed triple-negative breast cancer.

National Comprehensive Cancer Network guidelines recommend (18)F-FDG-PET/CT, in addition to standard staging procedures, for systemic staging of newly diagnosed stage III breast cancer patients. However, factors in addition to stage may influence PET/CT utility. As breast cancers that are negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (triple-negative breast cancer, or TNBC) are more aggressive and metastasize earlier than other breast cancers, we hypothesized that receptor expression may be one such factor. This study assesses (18)F-FDG-PET/CT for systemic staging of newly diagnosed TNBC. In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with TNBC who underwent (18)F-FDG-PET/CT in 2007-2013 prior to systemic or radiation therapy. Initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery, if performed prior to (18)F-FDG-PET/CT. (18)F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases, as well as unsuspected synchronous malignancies. Kaplan Meier survival estimates were calculated for initial stage IIB patients stratified by whether or not stage 4 disease was detected by (18)F-FDG-PET/CT. A total of 232 patients with TNBC met inclusion criteria. (18)F-FDG-PET/CT revealed unsuspected distant metastases in 30 (13%): 0/23 initial stage I, 4/82 (5%) stage IIA, 13/87 (15%) stage IIB, 4/23 (17%) stage IIIA, 8/14 (57%) stage IIIB, and 1/3 (33%) stage IIIC. Twenty-six of 30 patients upstaged to IV by (18)F-FDG-PET/CT were confirmed by pathology, with the remaining four patients confirmed by follow-up imaging. In addition, seven unsuspected synchronous malignancies were identified in six patients. Initial stage 2B patients who were upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival compared to initial stage 2B patients who were not (3-year Kaplan Meier estimate 0.33, 95% CI 0.13-0.55 versus 0.97, CI 0.76-0.93, p < .0001). F-FDG-PET/CT revealed distant metastases in 15% of patients with stage IIB TNBC. Stage IIB patients upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival than those who were not, consistent with (18)F-FDG-PET/CT detecting an increased burden of disease. This study provides further evidence that populations of patients with stage IIB breast cancer, such as TNBC, should be considered for systemic staging with (18)F-FDG-PET/CT at the time of initial diagnosis.

Cost-effectiveness of strain-targeted cardioprotection for prevention of chemotherapy-induced cardiotoxicity

BackgroundCancer chemotherapy increases the risk of heart failure. This cost-effectiveness model compared strain-guided cardioprotection with other protective strategies using a health care payer perspective and five-year time horizon. MethodsThree cardioprotection strategies were assessed: 1) usual care (EF-guided cardioprotection, EFGCP) with cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX), 2) universal cardioprotection (UCP) for all such patients, and 3) strain-guided cardioprotection (SGCP — treatment of patients with subclinical cardiotoxicity [S-CTX]). A Markov model, informed by the published literature on transitional probabilities, costs and quality-adjusted life years (QALYs) was developed to assess the incremental cost-effectiveness ratio (ICER). Costs, effects and ICER of each specified cardioprotective strategy were assessed over a 5-year range, with sensitivity analyses for significant variables. ResultsIn the reference case of a 49year old woman with stage IIb breast cancer treated with sequential anthracyclines and trastuzumab, strain-guided cardioprotection (3.79 QALYS and $4159 cost over 5years) dominated both UCP (3.64 QALYs and $5967 cost over 5years) and EFGCP (3.53 QALYs and $7033 cost over five years). Model results were dependent on the probabilities of patients developing subclinical LV dysfunction, with UCP dominating alternative strategies at probabilities ≥51%. Variations in the cost of cardioprotective medications and probabilities of cardioprotection side-effects had no effect on model conclusions. ConclusionsIn patients at risk of chemotherapy-related cardiotoxicity, strain-guided cardioprotection provides more QALYs at lower cost than standard care or uniform cardioprotection.

Locoregional Outcomes in Clinical Stage IIB Breast Cancer After Neoadjuvant Therapy and Mastectomy With or Without Radiation

Low rates of locoregional recurrence (LRR) in patients with clinical stage IIB breast cancer (cT2N1 or cT3N0) who undergo neoadjuvant therapy (NAT) and mastectomy have been reported. We aimed to quantify the risk of LRR and the relationship between LRR and potential risk factors in this subset of patients.We conducted a retrospective review of 116 patients with clinical IIB breast cancer who underwent NAT followed by mastectomy +/− postmastectomy radiotherapy (PMRT) between 2000 and 2009. We estimated the rate of LRR by cumulative incidence. The effect of prognostic factors was examined by Gray's test and Fine and Gray's test.Median follow-up: 63 months. Median age: 49. 28.4% cT2N1 and 71.6% cT3N0. 62.1% of tumors were ER+, 22.6% HER2+, 19% triple negative (TN). All patients underwent NAT and mastectomy. The majority of patients (87%) received PMRT; 32.3% were treated to chest wall (CW) only, and 67.7% to CW plus supraclavicular (SCV) field.Compared to cT2N1, patients with cT3N0 disease were more likely to be pN0 (60% vs 27%, P = 0.005). There was no significant relationship between risk of LRR and pathologic complete response (pCR), use of PMRT, RT to SCV field, or TN status, but there was higher risk of LRR in cT2N1 than cT3N0 (HR 6.03, P = 0.015).LRR was more common in cT2N1 than in cT3N0 disease, emphasizing the negative prognostic implication of clinically node-positive presentation.