International Journal of Breast Cancer最新文献

Purpose: To conduct an exploratory study to identify mechanisms that differentiate Luminal A (BT474 and MCF-7) and triple-negative (MDA-MB-231 and MDA-MB-468) breast cancer (BCa) cell lines to potentially provide novel therapeutic targets based on differences in energy utilization.

Methods: Cells were cultured in media containing either [U-¹³C]-glucose or [U-¹³C]-glutamine for 48 hours. Conditioned media and cellular extracts were analyzed by ¹H and ¹³C NMR spectroscopy.

Results: MCF-7 cells consumed the most glucose, producing the most lactate, demonstrating the greatest Warburg effect-associated energy utilization. BT474 cells had the highest tricarboxylic acid cycle (TCA) activity. The majority of energy utilization patterns in MCF-7 cells were more similar to MDA-MB-468 cells, while the patterns for BT474 cells were more similar to MDA-MB-231 cells. Compared to the Luminal A cell lines, TNBC cell lines consumed more glutamine and less glucose. BT474 and MDA-MB-468 cells produced high amounts of ¹³C-glycine from media [U-¹³C]-glucose which was integrated into glutathione, indicating de novo synthesis.

Conclusions: Stable isotopic resolved metabolomics using ¹³C substrates provided mechanistic information about energy utilization that was difficult to interpret using ¹H data alone. Overall, cell lines that have different hormone receptor status have different energy utilization requirements, even if they are classified by the same clinical BCa subtype; and these differences offer clues about optimizing treatment strategies.

Objectives: The aim of this study is to describe the characteristics and predictors of discontinuation during follow-up care among breast cancer patients at the Radiation Oncology Department, University College Hospital (UCH), Ibadan, Nigeria.

Methodology: This is a retrospective cross-sectional study of 504 patients with histological diagnosis of breast cancer referred for radiotherapy to the breast or chest wall. Data extraction form was used to obtain information on sociodemographic and disease related variables and time to discontinuation of care. Discontinuation rates and its predictors were estimated using Kaplan-Meier, Log rank test, and Cox's regression method of analyses.

Results: Five hundred and four breast cancer patients were studied. The mean age was 47.7years, 58.2% presented late with advanced stage disease, and 40% and 39% had metastasis and anaemia, respectively. Seventy-seven percent of patients discontinued follow-up care before completion of ten-year period. The 5-year and 10-year discontinuation rates were 69.8% and 92.6%, respectively. The median discontinuation time was 44 months. Discontinuers were more likely to be older than the age of 45years {HR=1.415; 95% CI= 1.044 - 1.917}, have metastasis {HR=1.793; 95% CI=1.396 - 2.302}, be anaemic {HR=1.404; 95% CI = 1.120 - 1.760)}, and have late-stage disease {HR=1.310; 95% CI = 1.407-1.639)}.

Conclusion: Breast cancer care discontinuation is associated with late presentation and advanced stage of disease. Therefore a system of community follow-up care and public awareness about breast cancer symptoms is recommended to reduce late presentation and discontinuity of care.

Background: Breast cancer remains a serious public health problem globally. It is particularly increasing among adolescents and premenopausal women. Breast self-examination (BSE) is the most effective and feasible means of detecting breast cancer early in developing countries. This study aimed at evaluating and comparing knowledge of BSE among secondary and tertiary school students and at revealing their attitudes and practices about BSE.

Method: This cross-sectional study was conducted among 1036 female secondary and tertiary school students of Kwame Nkrumah University of Science and Technology and Technology Senior High School. Data was obtained using a pretested questionnaire to access sociodemography, knowledge, attitudes, and practice of BSE among the students.

Result: Most students were within the age of 15-24 years; 90.9% were aware of BSE. A high level of knowledge on BSE was found in 54.5% of the students. Knowledge was significantly higher in tertiary than secondary school students (p=0.002). 24.1% of the students thought BSE could be performed anytime; however only 8.1% of the students performed BSE monthly as recommended, whilst 41.8% had never practiced. Of these, more secondary students had never practiced BSE as compared to the tertiary students. 22.3% indicated they would wait for a change in a detected breast lump before seeking medical attention. 96.3% of the participants agree BSE is a good practice which must be encouraged.

Conclusion: Teaching of BSE should be intensified beginning at the high school level, emphasizing practice and its benefits for early detection of breast cancer.

During the multidisciplinary planning of postoperative therapy after breast cancer, borderline cases can arise with no clear rationale for or against adjuvant chemotherapy. In 50 hormone- receptor-positive, Her2neu-negative carcinomas of the breast with no or only minimal lymph node involvement (max. pT1a) we initiated an Oncotype DX® multigene assay in addition to the evaluation of usual parameters. In the oncology conference a vote for or against chemotherapy was taken on the basis of the conventional criteria for decision-making before the test results were available. The final recommendation was made after the multigene test. In 32 breast carcinomas (64%) a low recurrence score could be documented, while 26 (32%) showed an intermediate RS and 3 (6%) showed a high RS. In most cases the result of the test could validate the choice of therapy established using conventional criteria. In 5 cases the initial recommendation for adjuvant therapy was revised, and in 3 cases chemotherapy was secondarily recommended after evaluation of the test results. Conversely, in some cases a low or intermediate risk constellation did not argue against a recommendation for adjuvant chemotherapy. Altogether, the results of our study do not indicate that a multigene assay should be used as a routine diagnostic tool. Instead a thorough compilation and careful analysis of conventional parameters for therapeutic decision-making should take precedence, with special emphasis on histopathological and immunohistochemical results. In selected cases, however, a multigene assay can be a useful tool in the deliberation for or against a therapeutic pathway.

Background: To assess effectiveness of NPE, a proprietary Camellia sinensis nonfermentatum (CSNF) extract, in prevention and recovery of acute radiation-induced skin reaction (ARSR) and skin care during postoperative whole breast radiotherapy (RT).

Methods: Twenty patients were enrolled in this single centre, prospective, open-label pilot study. The outcomes of 20 prospective data sets were compared with 100 retrospectively collected matched data sets derived from hospital records. The preventive CSNF gel (2.5%) was administered 1 to 2 hours before each session on the irradiated fields. The care CSNF lotion (0.4%) was administered as 7-day pretreatment after each RT session, twice daily between RT sessions, and 4 to 8 weeks thereafter. The control group was treated according to the hospital care guidelines. The primary endpoint was time to ARSR ≥ Grade 2 (CTCAE v4.03); secondary endpoints were frequencies of ARSR grades 1, 2, 3, and 4, recovery of ARSR, frequencies of interruption and RT stop, complications and required rescue interventions, and tolerability of CSNF.

Results: Time to ARSR ≥ G2 (censoring) was significantly longer (p = 0.014) in the CSNF group. The hazard ratio was 2.33 (95% CI: 1.15-4.72), demonstrating a 50% decrease in the risk of developing ARSR ≥ G2. There was a trend to faster recovery from ARSR G2 in the CSNF group (100% versus 47%; p = 0.078). The proportion of patients requiring rescue treatment during RT and follow-up was markedly higher in the control compared to the CSNF group (1% to 51% versus 0% to 15%). CSNF gel and lotion were well tolerated both during and after RT.

Conclusions: This pilot study provides the first evidence on the potential pharmacological effectiveness of CSNF extract in prevention of RT-induced ARSR and recovery of skin irritation in patients undergoing postoperative whole breast RT and may reflect a novel concept for prevention of RT-induced ARSR and care of irritated skin.

Triple positive breast cancers overexpress both the human epidermal growth factor receptor 2 (HER2) oncogene and the hormonal receptors (HR) to estrogen and progesterone. These cancers represent a unique therapeutic challenge because of a bidirectional cross-talk between the estrogen receptor alpha (ERα) and HER2 pathways leading to tumor progression and resistance to targeted therapy. Attempts to combine standard of care HER2-targeted drugs with antihormonal agents for the treatment of HR+/HER2+ breast cancer yielded encouraging results in preclinical experiments but did improve overall survival in clinical trial. In this review, we dissect multiple mechanisms of therapeutic resistance typical of HR+/HER2+ breast cancer, summarize prior clinical trials of targeted agents, and describe novel rational drug combinations that include antihormonal agents, HER2-targeted drugs, and CDK4/6 inhibitors for treatment of the HR+/HER2+ breast cancer subtype.

Background: Inflammatory breast cancer (IBC) is a rare but most aggressive breast cancer subtype. The impact of locoregional therapy on survival in IBC is controversial.

Methods: Patients with nonmetastatic IBC between 1988 and 2013 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry.

Results: We identified 7,304 female patients with nonmetastatic inflammatory breast cancer (IBC) who underwent primary tumor surgery. Most patients underwent total mastectomy with only 409 (5.6%) undergoing a partial mastectomy. In addition, 4,559 (62.4%) were also treated with radiation therapy. The patients who underwent mastectomy had better survival compared to partial mastectomy (49% versus 43%, p = 0.003). The addition of radiation therapy was also associated with improved 5-year survival (55% versus 40%, p < 0.001). Multivariate analysis showed that black race HR (1.22, 95% CI 1.18-1.35), ER negative status (HR 1.22, 95% CI 1.16-1.28), and higher grade (HR 1.14, 95% CI 1.07-1.20) were associated with poor outcome. Cox proportional hazards model showed that total mastectomy (HR 0.75, 95% CI 0.65-0.85) and radiation (HR 0.64, 95% CI 0.61-0.69) were associated with improved survival.

Conclusions: Optimal locoregional therapy for women with nonmetastatic IBC continues to be mastectomy and radiation therapy. These data reinforce the prevailing treatment algorithm for nonmetastatic IBC.

Introduction: Accurate evaluation of estrogen and progesterone receptors and HER2 is critical when diagnosing invasive breast cancer for optimal treatment. The current evaluation method is via immunohistochemistry (IHC). In this paper, we compared results of ER, PR, and HER2 from microarray gene expression to IHC in 81 fresh breast cancer specimens.

Methods: Gene expression profiling was performed using the GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix Inc). Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 status was performed using standard methods at a CAP-accredited pathology laboratory. Concordance rates, agreement measures, and kappa scores were calculated for both methods.

Results: For ER, Kappa score was 0.918 (95% CI, 0.77.3-1.000) and concordance rate was 97.5% (95% CI, 91.4%-99.7%). For PR, Kappa score was 0.652 (95% CI, 0.405-0.849) and concordance rate was 86.4% (95% CI, 77%-93%). For HER2, Kappa score was 0.709 (95% CI, 0.428-0.916) and concordance rate was 97.5% (95% CI, 91.4%-99.7%).

Conclusion: Our results are in line with the available evidence with the concordance rate being the lowest for the progesterone receptor. In general, microarray gene expression and IHC proved to have high concordance rates. Several factors can increase the discordance rate such as differences in sample processing.

Radiation therapy is a mainstay of treatment in early and locally advanced breast cancer but is typically reserved for palliation of symptomatic lesions in patients with metastatic breast cancer. With new advances in the field of tumor biology and immunology, the role of radiation in the metastatic setting is evolving to harness its immune-enhancing properties. Through the release of tumor antigens, tumor DNA, and cytokines into the tumor microenvironment, radiation augments the antitumoral immune response to affect both the targeted lesion and distant sites of metastatic disease. The use of immunotherapeutics to promote antitumoral immunity has resulted in improved treatment responses in patients with metastatic disease and the combination of radiation therapy and immunotherapy has become an area of intense investigation. In this article, we will review the emerging role of radiation in the treatment of metastatic disease and discuss the current state of the science and clinical trials investigating the combination of radiation and immunotherapy.