Treatment and outcomes of patients with primary breast sarcoma

Background

Surgery is the main treatment for primary breast sarcoma (PBS). Here we characterize this disease and determine factors associated with use of adjuvant therapy.

Methods

Records of patients with PBS from 1986 to 2006 were reviewed. Overall survival (OS) was estimated by Kaplan-Meier. Relationships between patient variables and OS were determined using univariate Cox proportional hazard models.

Results

Thirteen patients with PBS were identified; 10 patients underwent mastectomy, and 3 underwent partial mastectomy. Six patients underwent axillary staging; none were positive. Patients with tumors >5 cm were more likely to undergo radiation therapy (P <.05). Local recurrence occurred in 7 patients. Metastatic disease was present in 2 patients at diagnosis, and 6 patients developed metastatic disease; all 8 patients died from their disease. Five patients remained disease free. Five-year OS was 67% (83% for tumors <5 cm and 42% for tumors >5 cm). Tumor size was significantly associated with OS (relative risk = 1.1/1 cm increase in size > 5 cm).

Conclusions

Treatment for PBS is excision to clear margins. Axillary staging is not indicated. Tumor size >5 cm is the only significant prognostic indicator of overall survival.     

29例乳腺肉瘤临床治疗分析

为探讨乳腺肉瘤临床最佳治疗方案,作者对１９６４年３月至１９９４年５月收治的２９例乳腺肉瘤的临床资料进行了回顾性分析。随诊４个月至２５年。７例死亡,９例复发;１５例存活１０年以上,５例存活２０年以上。作者认为,本病多需病理证实,以手术治疗为主,无论低度或高度恶性,均应采取包括肿瘤周围正常组织的广泛切除;对复发病例不应放弃再次手术机会;对临床未能触及肿大淋巴节者可不予清扫腋下淋巴节。     

Effects of locoregional radiotherapy in patients with metastatic breast cancer

ObjectivesThis study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site.Material and methodsBetween 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation.Results2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 ± 2.4 months and 45.1 ± 2.9 months, respectively. Three- and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001).ConclusionRT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1–3 metastatic sites), and the use of hormone therapy.     

Comparison of outcomes between metaplastic and triple-negative breast cancer patients

PurposeMetaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC.MethodsThe National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS.ResultsAltogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS.ConclusionsMBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein.     

Radiotherapy in the treatment of breast cancer: a personal retrospective

Allan Langlands commenced training as a radiation oncologist in 1960 and has continued to treat patients with breast cancer for over 30 years. Moved to Westmead Hospital in Sydney he played a role in the development of radiation oncology in Australia. With an extensive research record (authoring over 200 peer-reviewed papers) this article reflects the changes in breast cancer treatment which have occurred over this period. The incorporation of evidence from the clinical trials in breast cancer management, changes in radiation therapy techniques and incorporation of patient choice in treatment decisions are discussed.     

Locoregional recurrence in patients with HER2 positive breast cancer

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes.     

Trends in surgical treatment of breast cancer at Mayo Clinic 1980-2004

The study encompassed the time period January 1980 through December 2004. During this time 9485 women underwent mastectomy, 6847 women underwent breast conserving surgery (BCS) and 2477 women underwent breast radiotherapy (RT) for breast cancer. Linear regression modeling was used to quantify the rate of change in the proportion of women undergoing mastectomy during specific time periods. Chi-square tests were used to compare the proportion of women with a breast cancer less than 3 cm in size undergoing mastectomy the year prior to and the year after a specific event.There was a significant decrease in the number and proportion of mastectomies performed, an increase in the number of BCS procedures performed and an increase in the number of women undergoing breast RT around the times of (1) the employment of a young surgeon trained in BCS, (2) publication of the NIH Consensus Statement and (3) establishment of a multidisciplinary Breast Clinic.     

Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results

GoalsTo assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not.MethodsThe SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973–2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4.Principle resultsThere were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19–1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31–1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods.ConclusionThere was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods.     

Integration of radiation and immunotherapy in breast cancer - Treatment implications

Radiation therapy (RT) has been successfully used in the treatment of breast cancer (BC) for over a century. While historically thought to be immunosuppressive, new data have shown that RT can work together with the immune system to eliminate cancer. It can cause immunogenic cell death and facilitate tumor neoantigen presentation and cross-priming of tumor-specific T-lymphocytes, turning irradiated tumor into an in-situ vaccine. Unfortunately, due to various immune escape mechanism put in place by the tumor, RT alone rarely results in a systemic response of metastatic disease sites (known as the abscopal effect). Immunotherapy, a series of agents designed to stimulate the immune system in order to generate tumor-specific immune response, is showing promise in treatment of various cancers, including BC, and can be an ideal complement to RT in stimulating a systemic immune response to reject the tumor cells. This review discusses the mechanisms in which RT can trigger an immune response for tumor rejection, and provide emerging preclinical and clinical data of combination immunoradiotherapy, and its potential in treating BC.     

Underdiagnosed and disfiguring - Radiation-induced morphea following breast cancer treatment

ObjectivesRadiation-induced morphea (RIM) is a rare, painful and disfiguring complication in women who receive adjuvant radiotherapy treatment for breast cancer. It is a distinct entity unrelated to radiation-induced fibrosis of the breast.Materials and methodsBetween the years 2005–2016, approximately 12,000 breast cancer cases were treated with surgery and radiation in the central district of Israel. From that population, we have identified and managed the cases of breast RIM by a multidisciplinary team of dermatologists, breast surgeons, and plastic surgeons. Demographic, oncologic, diagnostic and treatment data were collected and reviewed.ResultsThree cases of breast radiation-induced morphea, with an estimated prevalence of 1:3000 cases of post-breast cancer radiation where identified. The first signs of morphea appeared years after the completion of standard RT. Early management leads to superior cosmetic results.ConclusionsUnfortunately, there are no known predictors for RIM. Early recognition by the oncologist, the breast surgeon or the reconstructive surgeon during follow-up enables expeditious provision of patient reassurance and helps guide potential treatment options.     

贝伐单抗对乳腺癌皮下移植瘤放疗的增敏作用及其机制

目的 观察贝伐单抗对乳腺癌皮下移植瘤放射治疗的影响并探讨其机制.方法 将30只建立皮下移植瘤裸鼠随机分为贝伐单抗联合放射治疗组、单纯放射治疗组、正常组,相应处理后绘制生长曲线,Western blot法及免疫组织化学法检测各组缺氧诱导因子(HIF)-1α、血管内皮生长因子(VEGF)、细胞核增殖抗原(Ki-67)、CD31的表达.结果 联合组皮下移植瘤退缩更为显著(P＜0.05);免疫组织化学显示联合组Ki-67表达最弱,HIF-1 α、CD31表达也较单纯放射治疗组减弱,差异有统计学意义(P＜0.05);Western blot显示联合组HIF-1α、VEGF表达最弱.结论 贝伐单抗在乳腺癌皮下移植瘤放射治疗中发挥放射治疗增敏作用,可能是通过抑制HIF-1α、VEGF表达从而抑制肿瘤细胞增殖及肿瘤组织内血管形成来实现的.     

Reirradiation for locally recurrent breast cancer

The aim of this study is to review the current status of reirradiation therapy (Re-RT) for locally recurrent breast cancer. The overall outcome of breast/chest wall Re-RT is difficult to assess because of the wide range of different treatments that a patient may have undergone and the patient's individual features. The local control and complete response rates were reported to be 43–96% and 41–71%, respectively. The combination of Re-RT and hyperthermia seems to be related to improved outcomes. Toxicity rates vary between studies, and Re-RT is generally well tolerated. Re-RT may be considered an option for patients with breast cancer relapse after prior irradiation. Further studies are needed to determine the best irradiation volume and treatment modality for patients with locally recurrent disease.     

The impact on clinical outcomes of post-operative radiation therapy delay after neoadjuvant chemotherapy in patients with breast cancer: A multicentric international study

IntroductionRadiation therapy (RT) is frequently used for post-operative treatment in breast cancer (BC) patients who received preoperative systemic therapy (PST) and surgery. Nevertheless, the optimal timing to start RT is unclear.Material and methodsData from BC patients who underwent chemotherapy as PST, breast surgery and RT at 3 Institutions in Brazil and Canada from 2008 to 2014 were evaluated. Patients were classified into three groups regarding to the time to initiation of RT after surgery: <8 weeks, 8–16 weeks and >16 weeks.ResultsA total of 1029 women were included, most of them (59.1%; N = 608) had clinical stage III. One hundred and forty-one patients initiated RT within 8 weeks, 663 between 8 and 16 weeks and 225 beyond 16 weeks from surgery. With a median follow-up of 32 months, no differences in disease-free survival (DFS), overall survival and locoregional recurrence-free survival (LRRFS) were observed of time to indicated RT (<8 weeks versus 8–16 weeks versus >16 weeks). However, in luminal subtype patients (46.5%; N = 478), initiation of RT up to 8 weeks after surgery was associated with better LRRFS (<8 weeks versus >16 weeks: HR 0.22; 95%CI 0.05–0.86; p = 0.03), with a tendency to a better DFS (<8 weeks versus >16 weeks: HR 0.50; 95%CI 0.25–1.00).ConclusionRT initiated up to 8 weeks after surgery was related to better LRRFS in luminal BC patients who underwent PST. Our results suggest that early start of RT is important for these patients.     

Noncompliance with adjuvant radiation, chemotherapy, or hormonal therapy in breast cancer patients

INTRODUCTION: There is little information on patient-driven noncompliance of adjuvant therapies and its consequences. METHODS: This retrospective study compares clinical, pathological features and outcomes of breast cancer patients who were compliant to recommended radiation, chemotherapy, and hormonal therapies to those who were noncompliant. RESULTS: Noncompliance rates for chemotherapy, radiation, and tamoxifen were 31 of 421 (7%), 30 of 855 (4%), and 294 of (37%) respectively. Old age was associated with noncompliance to chemotherapy and radiation, but younger women tend to be more often noncompliant to tamoxifen. Noncompliance with chemotherapy or radiation did not significantly affect 5-year local and distant disease-free survival rates. Noncompliance with tamoxifen was associated with decreased 5-year local and distant disease-free survivals (87% versus 96%, 76% versus 87%, respectively, P < .001). CONCLUSION: Noncompliance with tamoxifen is the most common, resulting in significantly increased risk of local and distant disease recurrence.     

乳癌放疗后放射性溃疡的治疗

目的　探讨乳癌放射性治疗 (下简称放疗 )后放射性溃疡的治疗方法 ,阐述放疗后臂丛神经损伤的广泛性和严重性。方法　 1999年以来分别应用腹直肌肌皮瓣转移、皮肤软组织扩张、局部皮瓣转移和局部延迟皮瓣转移等方法修复乳癌放疗后放射性溃疡 16例 ,并常规行肌电图检查了解臂丛神经损伤的情况。结果　除 1例患者因创口感染而皮瓣部分坏死外 ,其余皮瓣成活良好 ,创面修复满意 ;10例行肌电图检查的患者中 ,有 7例合并有臂丛神经损伤。结论　乳癌放疗后引起的放射性溃疡常伴有臂丛神经损伤 ,这些损伤呈慢性、进行性和不可逆性改变 ;应用血运良好的皮瓣可有效地修复溃疡创面。     

Mammographic density and prognosis in primary breast cancer patients

PurposeMammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients.MethodsA total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status.ResultsAfter median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect.ConclusionsAlthough MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.     

Portrait,treatment choices and management of breast cancer in nonagenarians: An ongoing challenge

There are only scarce data on the management of nonagenarians with breast cancer, and more particularly on the place of radiation therapy (RT). We report a retrospective study on patients aged 90 years old or older, with breast cancer, receiving RT.Records from RT departments from five institutions were reviewed to identify patients 90 years old of age and older undergoing RT over past decade for breast cancer. Tumors' characteristics were examined, as well treatment specificities and treatment intent.44 patients receiving RT courses were identified, mean age 92 years. Treatment was given with curative and palliative intent in 72.7% and 27.3% respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery, and tumor stage. Median total prescribed dose was 40 Gy (23–66). Hypo fractionation was used in 77%. Most toxicities were mild to moderate. RT could not be completed in 1 patient (2.3%). No long-term toxicity was reported. Among 31 patients analyzable for effectiveness, 24 patients (77.4%) had their diseased controlled until last follow-up, including 17 patients (54.8%) experiencing complete response. At last follow-up, 4 patients (12.9%) were deceased, cancer being cause of death for two of them.The study shows that breast/chest RT is feasible in nonagenarians. Although the definitive benefit of RT could not be addressed here, hypofractionated therapy allowed a good local control with acceptable side effects.     

Low risk of recurrence in elderly patients treated with breast conserving therapy in a single institute

ObjectivesTo guide decision making in preventing over- or under-treatment in older breast cancer patients who have undergone breast conserving surgery, we analyzed prognostic factors and risk of recurrence in a consecutive series of patients ≥ 65 years old with breast cancer and identified subgroups that may benefit or not from more intensive treatment.MethodsPatients ≥65 years of age with breast cancer (pT1-2/pN0-2) treated with breast conserving surgery and postoperative radiation therapy at the Netherlands Cancer Institute (NKI) between 1980 and 2008 were identified. Endpoints were locoregional recurrence (LRR), distant metastasis (DM) and overall survival (OS). Multivariable analyses were performed using Cox proportional hazards models.Results1922 patients with a median age of 70 years were analyzed. The 5- and 10- years LRR rates were 2% and 3% respectively. In multivariable analysis there was no significant factor influencing LRR risk. Patients with low risk tumors (node negative patients with T1 and ER positive, grade 1 or 2) had lower risk of DM (HR 0.26) and better OS (HR 0.65) compared to patients with higher risk tumors (grade 3 and/or node positive).ConclusionIn elderly breast cancer patients the risk of LRR and DM is low. In patients with less favorable characteristics the risk of LRR is equally low, with a higher risk to develop DM and worse OS. Treatment in the low risk group may be minimized, while for the higher risk group adjuvant treatment could be intensified.