Treatment Of Early-stage Breast Cancer Research Articles

Surgical management of breast cancer in China: the Fudan University Shanghai Cancer Center experience

Breast cancer is the most frequently diagnosed cancer in Chinese women, and early-stage patients are significantly increasing. Surgery is the main treatment for early-stage breast cancer with the “minimally invasive procedures” concept. The modality of breast cancer surgery has changed greatly in recent years in China, especially in our cancer center, Fudan University Shanghai Cancer Center (FUSCC). Firstly, pre-surgery biopsy is a routine procedure, which is mainly assisted by imaging instruments. Secondly, the number of breast-conserving surgery (BCS) and simple mastectomy procedures with or without sentinel lymph node biopsy (SM ± SLNB) is increasing gradually; radical mastectomy (RM) and modified radical mastectomy (MRM) are decreasing annually. Thirdly, SLNB has become a routine procedure in our center; it is safe and effective for replacing axillary lymph node dissection (ALND). Finally, reconstruction surgery has progressively advanced, although the operation cases are limited. This review article looks back at the development of breast cancer surgery, highlights the hallmarks of surgical management in our center as well as in China and discusses the future necessary efforts to improve the outcome and life quality for Chinese patients.

Optimal duration of adjuvant chemotherapy for high-risk node-negative (N–) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106)

PurposeOptimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. Patients and methodsBetween 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(−) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER– and PR–), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. ResultsAt 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89–1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91–2.13], P = .12). ConclusionDifferences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. Clinical trial registry numberNCT00055679, Agence National de Sécurité du Médicament (ANSM) – France.

Intraoperative Radiation (IORT) as Adjuvant Radiation Monotherapy for Early-Stage Breast Cancer Patients Treated with Breast Conserving Surgery

Partial Breast irradiation is now an appropriate technique for delivering adjuvant radiation for properly selected patients who undergo breast conserving treated. We report the clinical outcomes for such patients treated at Exeter Hospital with electronic 50Kv brachytherapy alone as Adjuvant Radiation Treatment for Early-Stage Breast Cancer.

Breast cancer cell targeted MR molecular imaging probe: Anti-MUC1 antibody-based magnetic nanoparticles

Effective and specific diagnostic imaging techniques are important in early-stage breast cancer treatment. The objective of this study was to develop a specific breast cancer contrast agent for magnetic resonance imaging (MRI). In so doing, superparamagnetic iron oxide nanoparticles (SPIONs) were conjugated to C595 monoclonal antibody using EDC chemistry to produce nanoprobe with high relaxivity and narrow size (87.4±0.7 nm). To test the developed nanoprobe in vitro, assessments including Cell toxicity, targeting efficacy, cellular binding, and MR imaging were carried out. The results indicated that after 6 hrs incubation with MCF-7 cells at 200 to 25 µg Fe/ml doses, 76% to 16% T2 reduction was obtained. The presence of iron localised in MCF-7 cells measured by atomic absorption spectroscopy (AAS) was about 9.95±0.09 ppm iron/cell at higher doses of nanoprobe. Moreover, a linear relationship between iron concentration of nontoxic SPION-C595 and T2 relaxation times was observed. This study also revealed that developed nanoprobe might be used as a specific negative contrast agent for detecting breast cancer.

Early stage breast cancer treatment and prognostic factors: Post San Antonio Breast Cancer Symposium 2016.

SummaryDevelopments in early breast cancer presented at the 2016 San Antonio Breast Cancer Symposium included important studies on extending adjuvant endocrine therapy with aromatase inhibitors, the role of bisphosphonates, and evidence for molecular prognostic factors and circulating tumor cells in early stage breast cancer patients.

Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review.

Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment. In metastatic disease, it is currently considered the first-line treatment for postmenopausal women with estrogen receptor-positive breast tumors. Anastrozole has shown promising results in the adjuvant treatment of early-stage breast cancer in postmenopausal women. It has also achieved interesting results in the chemoprevention of the disease. Therefore, due to the importance of anastrozole both for endocrine treatment and chemoprevention of hormone-sensitive breast cancer in postmenopausal women, we proposed the current literature review in the SciELO and PubMed database of articles published in the last 10 years.

Polymeric composite devices for localized treatment of early-stage breast cancer.

For early-stage breast cancers mastectomy is an aggressive form of treatment. Therefore, there is a need for new treatment strategies that can enhance the use of lumpectomy by eliminating residual cancer cells with limited side effects to reduce local recurrence. Although, various radiotherapy-based methods have been developed, residual cells are found in 20–55% of the time at the first operation. Furthermore, some current treatment methods result in poor cosmesis. For the last decade, the authors have been exploring the use of polymeric composite materials in single and multi-modal implantable biomedical devices for post-operative treatment of breast cancer. In this paper, the concept and working principles of the devices, as well as selected results from experimental and numerical investigations, are presented. The results show the potential of the biomedical implants for cancer treatment.

Abstract P6-09-19: Breast density change at 6 months is associated with change at 12 months as measured by fat-water decomposition MRI in women on tamoxifen

Abstract P6-09-19: Breast density change at 6 months is associated with change at 12 months as measured by fat-water decomposition MRI in women on tamoxifen

Disparities in the Initial Local Treatment of Older Women with Early-Stage Breast Cancer: A Population-Based Study.

Although breast cancer is most prevalent among older women, the majority are diagnosed at an early stage. When diagnosed at an early stage, women have the option of breast-conserving surgery (BCS) plus radiation therapy (RT) or mastectomy for the treatment of early-stage breast cancer (ESBC). Omission of RT when receiving BCS increases the risk for recurrence and poor survival. Yet, a small subset of older women may omit RT after BCS. This study examines the current patterns of local treatment for ESBC among older women. This study conducted a retrospective observational analysis using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset of women age ≥66 diagnosed with stage I-II breast cancer in 2003-2009. SEER-Medicare data was additionally linked with data from the Area Resource File (ARF) to examine the association between area-level healthcare resources and treatment. Two logistic regression models were used to estimate how study factors were associated with receiving (1) BCS versus BCS+RT and (2) Mastectomy versus BCS+RT. A stratified analysis was also conducted among women aged <70 years. Among 45,924 patients, 55% received BCS+RT, 23% received mastectomy, and 22% received BCS only. Women of increasing age, comorbidity, primary care provider visits, stage II disease, and nonwhite race were more likely to have mastectomy or BCS only, than BCS+RT. Women diagnosed in 2004-2006, treated by an oncology surgeon, residing in metro areas, areas of greater education and income, were less likely to receive mastectomy or BCS only, than BCS+RT. While women aged <70 years were more likely to receive BCS+RT, socioeconomic and physician specialties were associated with receiving BCS only. Over half of older women with ESBC initially receive BCS+RT. The likelihood for mastectomy and BCS only increases with age, comorbidity, and vulnerable socio-demographic characteristics. Findings demonstrate continued treatment disparities among certain vulnerable populations.

Women With Breast Cancer Who Work For Accommodating Employers More Likely To Retain Jobs After Treatment.

Breast cancer affects one in eight women across the United States, and low-income minority survivors of breast cancer are at increased risk of job loss, compared to higher-income white survivors. Employer accommodations, such as schedule flexibility, have been associated with job retention in higher-income whites, but the role of such accommodations in job retention among low-income minorities is not well understood. We conducted a longitudinal study of 267 employed women ages18-64 who were undergoing treatment for early-stage breast cancer and spoke English, Chinese, Korean, or Spanish. We categorized patients by income level and by race/ethnicity. The category with the lowest job retention after treatment was low-income women (57percent). Job retention varied widely by race/ethnicity, ranging from 68percent among Chinese women to 98percent among non-Latina whites. Women who had accommodating employers were more than twice as likely to retain their jobs as those without accommodating employers. Low-income women were less likely than higher-income women to have accommodating employers, however. More uniform implementation of accommodations across low- and high-paying jobs could reduce disparities in employment outcomes among workers with a cancer diagnosis. Additional research is needed to better understand the barriers that employers, particularly those with low-income workers, may face in providing accommodations.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

Toevaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30Gy in 5 fractions and was escalated by 2.5Gy total for each cohort to 40Gy. In all, 75 patients were enrolled, with a median age of 62years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Dose was escalated to the target dose of 40Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

The Feasibility Study of a Hybrid Coplanar Arc Technique Versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost.

This study demonstrated the feasibility and advantages of a hybrid, volumetric arc therapy technique that used two 90° coplanar arcs and two three-dimensional conformal tangential beams in the simultaneous-integrated boost radiotherapy of left-sided breast cancer after breast-conserving surgery. A total of nine patients with stage I, left-sided breast cancer who underwent breast-conserving surgery were selected for this retrospective study. For each patient, a hybrid arc plan was generated and then compared with two hybrid intensity-modulated radiotherapy plans. All plans were optimized using the same objectives and dose constraints. The prescription dose was 50.4 Gy to the planning target volume with simultaneous boost to 60 Gy to the expanded gross target volume in 28 fractions. The differences among these hybrid plans were analyzed by the Kolmogorov–Smirnov test or the Wilcoxon rank sum test. The hybrid arc plans achieved the clinical requirements of target dose coverage and normal tissue (NT) dose constraints. It was found that the hybrid arc plans showed advantages in the conformity index of the expanded gross target volume, the V5 of the heart, the D2 of the left ventricle, and the D2 and V50.4 of NTs. The average beam-on time and monitor units of the hybrid arc plans were significantly lower (P < 0.001).

Reference to: Chen YG, Li AC, Li WY, Huang MY, Li XB, Chen MQ, et al. The Feasibility Study of a Hybrid Coplanar Arc Technique versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost. J Med Phys 2017;42:1-8.

Reference to: Chen YG, Li AC, Li WY, Huang MY, Li XB, Chen MQ, et al. The Feasibility Study of a Hybrid Coplanar Arc Technique versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost. J Med Phys 2017;42:1-8.

Response to the comments on "The Feasibility Study of a Hybrid Coplanar Arc Technique versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost. J Med Phys 2017;42:1-8".

Response to the comments on "The Feasibility Study of a Hybrid Coplanar Arc Technique versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost. J Med Phys 2017;42:1-8".

Objective decision making between conventional and oncoplastic breast-conserving surgery or mastectomy: An aesthetic and functional prospective cohort study

BackgroundBreast-conserving surgery (BCS) is considered the standard treatment for early-stage breast cancer. However, fair to poor cosmetic outcomes following conventional BCS have been observed in as many as one-third of cases. The aim of this study was to determine the critical tumor-to-breast volume ratio for each quadrant of the breast beyond which conventional BCS would no longer offer acceptable cosmetic and functional results or satisfactory quality of life for the patient. MethodsA prospective cohort study was performed between December 2011 and December 2013 involving 350 patients younger than 70 years with early-stage unifocal (T ≤ 30 mm) breast cancer who underwent wide excision and axillary sentinel lymph node biopsy followed by whole-breast irradiation. Using validated panels and software (the Breast Cancer Treatment Outcome Scale [BCTOS], EORTC Cancer Quality of Life Questionnaire number C30-BR23, and Breast Cancer Conservative Treatment – cosmetic results [BCCT.core] software), quality of life and aesthetic and functional parameters and their changes in correlation to the percentage of breast volume excised were statistically analyzed. ResultsThe maximum percentages of breast volume that were resectable by conventional BCS without resulting in unacceptable aesthetic and functional outcomes or decreased quality of life were 18–19% in the upper-outer quadrant (p < 0.0001), 14–15% in the lower-outer quadrant (p < 0.0001), 8–9% in the upper-inner quadrant (p < 0.0001), and 9–10% in the lower-inner quadrant (p < 0.0001). ConclusionAided by the calculated cut-off values for each breast quadrant, breast surgeons might render more objective decisions regarding performing conventional BCS, using oncoplastic techniques or choosing mastectomy with immediate reconstruction.

Annual surveillance mammography after early-stage breast cancer and breast cancer mortality.

After treatment for early-stage breast cancer (bca), annual surveillance mammography (asm) is recommended based on the assumption that early detection of an invasive ipsilateral breast tumour recurrence or subsequent invasive contralateral primary bca reduces bca mortality. We studied women with unilateral early-stage bca treated by breast-conserving surgery from 1994 to 1997 who subsequently developed an ipsilateral recurrence or contralateral primary more than 24 months after initial diagnosis, without prior regional or distant metastases. Annual surveillance mammography was defined as 2 episodes of bilateral mammography 11-18 months apart during the 2 years preceding the ipsilateral recurrence or contralateral primary. The association between asm and bca death was evaluated using a Cox proportional hazards model. We identified 669 women who experienced invasive ipsilateral recurrence (n = 455) or a contralateral primary (n = 214) at a median interval of 53 months [interquartile range (iqr): 37-72 months] after initial diagnosis, 64.7% of whom had received asm during the preceding 2 years. The median interval between the 2 bilateral mammograms was 12.3 months (iqr: 11.9-13.0 months), and the median interval between the 2nd mammogram and histopathologic confirmation of ipsilateral recurrence or contralateral primary was 1.5 months (iqr: 0.8-3.9 months). Median followup after ipsilateral recurrence or contralateral primary was 7.76 years (iqr: 3.68-9.81 years). The adjusted hazard ratio for bca death associated with asm was 0.86 (95% confidence limits: 0.63, 1.16). Annual surveillance mammography was associated with a modestly lowered hazard ratio for bca death.

Relationship of systemic cytokine concentrations to cognitive function over two years in women with early stage breast cancer

Cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). While CRCI has been associated with linked to chemotherapy, there is increasing evidence that the condition may start prior to treatment and for some, remain unresolved after active treatment and into survivorship. Although the pathophysiology of the condition is complex, alterations in systemic cytokines, signaling molecules activated in response to infection or injury that trigger inflammation, are a possible mechanism linked to cognitive dysfunction in breast cancer and other conditions. Given the conflicting results in the literature, the lack of focus on domain specific cognitive testing, and the need for a longer time period given the multiple modalities of standard treatments for early-stage breast cancer, this longitudinal study was conducted to address these gaps. MethodsWe assessed 75 women with early-stage breast cancer at five points over two years, starting prior to the initial chemotherapy through 24months after chemotherapy initiation. Measures included a validated computerized evaluation of domain-specific cognitive functioning and a 17-plex panel of plasma cytokines. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations to each cognitive domain. ResultsLevels and patterns of cytokine concentrations varied over time: six of the 17 cytokines (IL-6, IL-12, IL-17, G-CSF, MIPS-1β, and MCP-1) had the most variability. Some cytokine levels (e.g., IL-6) increased during chemotherapy but then decreased subsequently, while others (e.g., IL-17) consistently declined from baseline over time. There were multiple relationships among cytokines and cognition, which varied over time. At baseline, elevated concentrations of G-CSF and reduced concentrations of IL-17 were associated with faster psychomotor speed. At the second time-point (prior to the mid-chemotherapy), multiple cytokines had significant associations with psychomotor speed, complex attention, executive function, verbal memory, cognitive flexibility, composite memory and visual memory. Six months after chemotherapy initiation and at the one-year point, there were multiple, significant relationships among cytokines and multiple cognitive. At two years, fewer significant relationships were noted; however, lower concentrations of IL-7, a hematopoietic cytokine, were associated with better psychomotor speed, complex attention, and memory (composite, verbal and visual). MCP-1 was inversely associated with psychomotor speed and complex attention and higher levels of MIP-1β were related to better complex attention. ConclusionLevels and patterns of cytokines changed over time and demonstrated associations with domain-specific cognitive functioning that varied over time. The observed associations between cytokines and cognitive performance provides evidence that not only prototypical cytokines (i.e., IL-6, TNF-α, and IL1-β) but also cytokines from multiple classes may contribute to the inflammatory environment that is associated with cognitive dysfunction. Future studies to better delineate the cytokine changes, both individually and in networks, are needed to precisely assess a mechanistic link between cytokines and cognitive function in women receiving treatments for breast cancer.

PCN177 - Development of a Global Model for the Economic Evaluation of Pharmacogenomics Tests for Early-Stage Breast Cancer Treatment

PCN177 - Development of a Global Model for the Economic Evaluation of Pharmacogenomics Tests for Early-Stage Breast Cancer Treatment

Disparities in Surgical Treatment of Early-Stage Breast Cancer Among Female Residents of Texas: The Role of Racial Residential Segregation

IntroductionEarly-stage breast cancer can be surgically treated by using mastectomy or breast-conserving surgery and adjuvant radiotherapy, also known as breast-conserving therapy (BCT). Little is known about the association between racial residential segregation, year of diagnosis, and surgical treatment of early-stage breast cancer, and whether racial residential segregation influences the association between other demographic characteristics and disparities in surgical treatment. MethodsThis was a retrospective study using data from the Texas Cancer Registry composed of individuals diagnosed with breast cancer between 1995 and 2012. The dependent variable was treatment using mastectomy or BCT (M/BCT) and the independent variables of interest (IVs) were racial residential segregation and year of diagnosis. The covariates were race, residence, ethnicity, tumor grade, census tract (CT) poverty level, age at diagnosis, stage at diagnosis, and year of diagnosis. Bivariate and multivariable multilevel logistic regression models were estimated. The final sample size was 69,824 individuals nested within 4335 CTs. ResultsAdjusting for the IVs and all covariates, there were significantly decreased odds of treatment using M/BCT, as racial residential segregation increased from 0 to 1 (odds ratio [OR] 0.47; 95% confidence interval [CI], 0.41-0.54). There was also an increased likelihood of treatment using M/BCT with increasing year of diagnosis (OR 1.14; 95% CI, 1.13-1.16). A positive interaction effect between racial residential segregation and race was observed (OR 0.56; 95% CI, 0.36-0.88). ConclusionResidents of areas with high indices of racial residential segregation were less likely to be treated with M/BCT. Racial disparities in treatment using M/BCT increased with increasing racial residential segregation.

A Simple and Effective Technique of Breast Remodelling After Conserving Surgery for Lower Quadrants Breast Cancer.

Quadrantectomy is an oncologically safe procedure for the treatment of early-stage breast cancer, but it often results in poor aesthetic outcomes such as breast shape deformity, which is more visible if the tumour is located in the lower pole. We recommend the use of the transverse incision, which retains the oncological advantages of the quadrantectomy while leading to better aesthetical results. We evaluated the clinical results of 24 patients with breast cancer who underwent quadrantectomy of the lower breast pole and volume replacement with remodelling through three posterior scorings from January 2012 to January 2014, with cosmetic evaluations performed according to the criteria set by the Japanese Breast Cancer Society. Minimum follow-up after surgery was 2years, with an average of 28.4months. Among treated patients, the percentage of complications was extremely low and the degree of satisfaction fairly good. Moreover, the assessment of the medical team matched patient self-assessments. Immediate breast reconstruction of a defect performed after a quadrantectomy of the lower breast pole using the "posterior scoring technique" provided better cosmetic results compared to the transposition of residual breast tissue. This technique provides reliable and reproducible results, and it also appears to be rather successful on patients with small-moderate breasts in the absence of a certain degree of ptosis, therefore increasing its already considerable appeal. This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .