Adjuvant Radiation Trials for High-Risk Breast Cancer Patients: Adequacy of Lymphadenectomy

Background: The recently published, widely publicized adjuvant radiation trials from Denmark and Canada concluded that the addition of postoperative radiotherapy (XRT) to modified radical mastectomy (MRM) and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal patients with breast cancer. Our thesis is that adequate lymphadenectomies were not performed in either study. Consequently, the conclusion to these studies is not applicable to those patients who have undergone adequate surgery.Methods: To better assess adequate lymph node yield from an MRM, a retrospective review was performed on 215 consecutive patients treated surgically for invasive breast cancer. Data from this review were compared with the surgical data from the above-mentioned radiotherapy trials.Results: In a group of 131 patients who had MRM, the average number of nodes removed was 26 (median, 25), and 75.5% of the specimens had 20 or more lymph nodes. In 73 patients who underwent segmental mastectomy with axillary lymph node dissection, both the average and the median number of lymph nodes removed were 24, and 68.9% had 20 or more nodes. These data compare to the Danish radiation trial in which a median of 7 lymph nodes were removed (with 76% of the patients having 9 or fewer lymph nodes in the specimen) and to the Canadian radiation trial in which a median of 11 lymph nodes were removed. In addition, in our breast cancer patients with positive nodes (84 of 204; 41.2%), 45.2.% (38 of 84) had more than three positive nodes compared with 29.8% in the Danish study and 35% in the Canadian study.Conclusions: Our surgical data are sufficiently different from those of the Danish and Canadian studies to indicate that, in those studies, incomplete lymph node dissections were performed and that residual disease was left behind in the axilla in some or all of the patients. The addition of XRT in the setting of residual axillary disease may compensate for an inadequate operation and yield an acceptable oncological result; however, these studies did not provide an adequate comparison with a well-performed MRM without XRT. In the absence of documented benefit, XRT should not be routinely added if a complete lymph node dissection has been performed.     

Utility of Breast Magnetic Resonance Imaging in Patients With Occult Primary Breast Cancer

Background Although carcinoma presenting as axillary metastases is assumed to be due to breast cancer, identification of the primary lesion may prove problematic. We investigated the ability of breast magnetic resonance imaging (MRI) to identify the primary tumor, thereby confirming the diagnosis and broadening treatment options. Methods From 1995 to 2001, 69 patients at our institution presented with occult primary breast cancer. All patients had negative breast examinations and mammograms and underwent breast MRI. Results Of 69 patients, 55 had axillary adenopathy without evidence of distant disease (stage II); 14 had stage IV disease. In patients with stage II disease, MRI revealed suspicious lesions in 76% (42 of 55). In 62% (26 of 42), the MRI finding proved to be the occult primary tumor. Of these, 58% (15 of 26) were candidates for breast conservation. MRI did not identify the primary tumor in 25 women; 12 underwent mastectomy. Cancer was found in 33% (4 of 12) of these. Thirteen patients were treated with primary breast irradiation; three were lost to follow-up, one developed distant disease, and nine were without evidence of disease with a median follow-up of 4.5 years. In women with stage IV disease, MRI identified the primary tumor in 5 of 9 patients with regional adenopathy and 2 of 5 patients with distant disease (overall 50%; 7 of 14). MRI identified the primary tumor in women with both mammographically dense (19 of 44; 43%) and less dense (10 of 20; 50%) breasts. Conclusions Breast MRI detects mammographically occult cancer in half of women with axillary metastases, regardless of breast density. MRI is a powerful tool for stage II and stage IV patients with occult primary breast cancer. Claire L. Buchanan, MD, is now at Swedish Cancer Institute, 500 17th Avenue, Seattle, WA 98108     

Timing of Surgical Intervention for the Intact Primary in Stage IV Breast Cancer Patients

Background Recent studies demonstrate improved progression-free survival (PFS) and improved overall survival (OS) with extirpation of the primary tumor in breast cancer patients who present with metastatic disease at initial diagnosis. The subset of patients who would most benefit from surgery remains unclear. This study evaluates the pathological attributes and optimum timing for surgery in patients who present with stage IV breast cancer and an intact primary. Methods Retrospective, single-institution review of all breast cancer patients between 1997 and 2002 presenting with an intact tumor and synchronous metastatic disease. Information collected included: demographics, tumor characteristics, metastatic sites, type/timing of surgery, and radiation/systemic therapy received. Patients initiated treatment within 3 months of their diagnosis. Patients were divided into three groups based on time interval from diagnosis date to surgery date. Disease progression and vital status at last follow-up were evaluated. Analysis of metastatic PFS (defined by progression of systemic disease) benefit in relation to surgical timing was performed. Results Multivariate analysis revealed patients having only one site of metastasis, negative margins, and Caucasian race had improved PFS. Further analysis revealed non-Caucasian patients more often underwent surgical intervention for palliation versus surgery for curative intent, possibly explaining their worse outcome. Patients who underwent surgery in the 3–8.9 month or later period had improved metastatic PFS. Conclusions: Surgical extirpation of the primary tumor in patients with synchronous stage IV disease is associated with improved metastatic PFS when performed more than 3 months after diagnosis. Resection should be planned with the intent of obtaining negative margins.     

Identifying High-Risk Triple-Negative Breast Cancer Patients by Molecular Subtyping

IntroductionTriple-negative breast cancer (TNBC) is considered the most aggressive type of breast cancer (BC) with limited options for therapy. TNBC is a heterogeneous disease and tumors have been classified into TNBC subtypes using gene expression profiling to distinguish basal-like 1, basal-like 2, immunomodulatory, mesenchymal, mesenchymal stem-like, luminal androgen receptor (LAR), and one nonclassifiable group (called unstable).ObjectivesThe aim of this study was to verify the clinical relevance of molecular subtyping of TNBCs to improve the individual indication of systemic therapy.Patients and MethodsMolecular subtyping was performed in 124 (82%) of 152 TNBC tumors that were obtained from a prospective, multicenter cohort including 1,270 histopathologically confirmed invasive, nonmetastatic BCs ({"type":"clinical-trial","attrs":{"text":"NCT 01592825","term_id":"NCT01592825"}}NCT 01592825). Treatment was guideline-based. TNBC subtypes were correlated with recurrence-free interval (RFI) and overall survival (OS) after 5 years of observation.ResultsUsing PAM50 analysis, 87% of the tumors were typed as basal with an inferior clinical outcome compared to patients with nonbasal tumors. Using the TNBCtype-6 classifier, we identified 23 (15%) of TNBCs as LAR subtype. After standard adjuvant or neoadjuvant chemotherapy, patients with LAR subtype showed the most events for 5-year RFI (66.7 vs. 80.6%) and the poorest probability of 5-year OS (60.0 vs. 84.4%) compared to patients with non-LAR disease (RFI: adjusted hazard ratio [aHR] = 1.87, 95% confidence interval [CI] 0.69–5.05, p = 0.211; OS: aHR = 2.74, 95% CI 1.06–7.10, p = 0.037).ConclusionMolecular analysis and subtyping of TNBC may be relevant to identify patients with LAR subtype. These cancers seem to be less sensitive to conventional chemotherapy, and new treatment options, including androgen receptor-blocking agents and immune checkpoint inhibitors, have to be explored.     

Results of MRI Screening for Breast Cancer in High-Risk Patients with LCIS and Atypical Hyperplasia

Background Magnetic resonance imaging (MRI) can detect breast cancer in high-risk patients, but is associated with a significant false-positive rate resulting in unnecessary breast biopsies. More data are needed to define the role of MRI screening for specific high-risk groups. We describe our experience with MRI screening in patients with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS). Methods We retrospectively reviewed data from our high-risk screening program prospective database for the period from April 1999 (when screening MRI was first performed at our institution) to July 2005. Patients with AH or LCIS demonstrated on previous surgical biopsy were identified. All patients underwent yearly mammography and twice yearly clinical breast examination. Additional screening MRI was performed at the discretion of the physician and patient. Results We identified 378 patients; 126 had AH and 252 had LCIS. Of these, 182 (48%) underwent one or more screening MRIs (mean, 2.6 MRIs; range, 1–8) during this period, whereas 196 (52%) did not. Those who had MRIs were younger (P < 0.001) with stronger family histories of breast cancer (P = 0.02). In MRI-screened patients, 55 biopsies were recommended in 46/182 (25%) patients, with 46/55 (84%) biopsies based on MRI findings alone. Cancer was detected in 6/46 (13%) MRI-generated biopsies. None of the six cancers detected on MRI were seen on recent mammogram. All six cancers were detected in five patients (one with bilateral breast cancer) with LCIS; none were detected by MRI in the AH group. Thus, cancer was detected in 5/135 (4%) of patients with LCIS undergoing MRI. The yield of MRI screening overall was cancer detection in 6/46 (13%) biopsies, 5/182 (3%) MRI-screened patients and 5/478 (1%) total MRIs done. In two additional MRI-screened patients, cancer was detected by a palpable mass in one, and on prophylactic surgery in the other and missed by all recent imaging studies. For 196 non-MRI-screened patients, 21 (11%) underwent 22 biopsies during the same period. Eight of 22 (36%) biopsies yielded cancer in seven patients. All MRI-detected cancers were stage 0–I, whereas all non-MRI cancers were stage I–II. Conclusion Patients with AH and LCIS selected to undergo MRI screening were younger with stronger family histories of breast cancer. MRI screening generated more biopsies for a large proportion of patients, and facilitated detection of cancer in only a small highly selected group of patients with LCIS.     

Breast Conserving Surgery after Primary Chemotherapy in Locally Advanced Breast Cancer

Purpose: Primary chemotherapy is being given in the treatment of locally advanced breast cancers (LABC), but a major concern is local recurrence after therapy. The aim of this study was to assess the role of breast conserving surgery (BCS) in patients with locally advanced breast cancer.

Material and Methods: Twenty-eight patients, presenting LABC (T any, N 012, M0) were treated with primary chemotherapy comprising of cyclophosphamide, doxorubicin and fluorouracil and then BCS followed by radiotherapy were examined between the years 1992-2002 retrospectively. Before neoadjuvant chemotherapy, seven patients (25%) were Stage IIB, 19 patients (68%) Stage IIIA and two patients (7%) Stage IiIB. Survival times and curves were established according to the Kaplan-Meier method and compared by means of the log-rank test. The chi-square test and log rank test were performed for univariate statistical analysis of each prognostic factor. P values in multivariate analysis were carried out by the Cox’s proportional hazards regression model. All p values were two-sided in tests and p values < 0.05 were considered significant.

Results: Clinical down staging was obtained in 25 (89%) of patients. Three (11%) patients had complete clinical response, 22 (78%) patients with partial response and 3 (11%) had stable disease. The primary tumour could not be palpated after chemotherapy in 6 (21%) of 28 patients presenting with palpable mass, therefore needle localization was performed for BCS. Median follow-up was 51.9 months (ranging 10 to 118 months). Local recurrence was detected in 4 (14%) patients. Distant metastasis developed in 5 (18%) patients. Three of the patients died of distant metastases and two of them are alive at 49 months. Five-year survival rate was 66%. Statistically, there were no significant factors in terms of local recurrence. Histological grade and menopause status were significantly associated with overall survival (p = 0.018) and nuclear grade was the one significant factor on distant disease-free survival in univariate analysis (p = 0.006). In multivariate analysis, there were no significant factors in terms of overall and distant disease-free survival Conclusions: Negative margin is more important than the clinical and histological parameters, such as pretreatment stage, clinical response rate, ER and PR in terms of local recurrence. BCS can be performed safely by achieving free surgical margin in patients who have small sized tumour and with either N2 axillary involvement or skin invasion.     

乳腺癌转移抑制基因1抑制乳腺癌转移的作用机理研究进展

目的综述乳腺癌转移抑制基因1（BRMS1）在抑制乳腺癌转移中的作用机理研究进展。方法采用文献回顾的方法，对目前国内、外有关BRMS1在乳腺癌中的研究状况加以分析与综述。结果BRMS1与其他肿瘤转移抑制基因一样，主要抑制肿瘤的转移，并不影响肿瘤的生长，在乳腺癌中主要通过调节细胞间的信号转导及其他转移抑制基因的表达而抑制乳腺癌的转移。结论对BRMS1基因的深入研究有助于进一步深化对乳腺癌转移的认识，为肿瘤转移的分子诊断和基因治疗提供新的思路。     

Physical Activity in the Prevention and Therapy of Breast Cancer

SUMMARY: Numerous epidemiological and case-control studies have proven the efficacy of physical activity in the prevention of breast cancer. In physically active subjects, the risk reduction averaged 25-30%. According to published data, 30-60 min of exercise per day at a moderate intensity is regarded as the optimal duration. Furthermore, physical activity plays an important role in the therapy of breast cancer, not only after finishing but already during treatment. Among experts, the evidence of a positive impact on the fatigue syndrome and on the quality of life is found sufficiently convincing. Now, the most recent investigations have shown that regular moderate exercise may bring about a prolongation of life. In the present publication, the most important background facts, potential mechanisms, and recommendations for the prevention and therapy of breast cancer are described.     

Radiotherapy-Induced Fatigue in Breast Cancer Patients

BackgroundA large proportion of breast cancer patients who undergo adjuvant radiotherapy suffer from radiotherapy-induced fatigue. The possible causative factors of this specific side effect are diverse.SummaryPrevalence, duration, and severity of radiotherapy-induced fatigue are dependent on the type of radiotherapy, as well as on the irradiated volume, dose scheme, on the number of radiation fields, the combination with other treatments, diurnal rhythm, smoking, and time-to-hospitalization. Recommended treatments include non-pharmacologic interventions, such as physical and psychosocial interventions. Pharmacologic therapies include treatment with methylphenidate and modafinil. In addition to its early detection with standardized instruments, adequate education to breast cancer patients about risks and predisposing factors of radiotherapy-induced fatigue is essential. Multidimensional strategies help to maintain the patients'' quality of life and therefore guarantee treatment adherence and efficacy.Key MessagesRadiotherapy-induced fatigue is an underreported, underdiagnosed, and undertreated side effect. This review provides an overview of radiotherapy-induced fatigue in breast cancer patients receiving adjuvant radiotherapy.     

家属参与模式对乳腺癌患者围术期并发症及乳房美观性的影响

目的 探讨家属参与模式对乳腺癌患者围术期并发症及乳房美观性的影响。方法 选择2022年 1月-10月于南京市妇幼保健院行乳腺癌手术的患者68例,随机分成对照组和观察组,每组34例。对照组行 常规护理,观察组在对照组基础上增加了家属参与模式,比较两组乳房美观评分、家庭关怀度、并发症发生 率。结果 观察组乳头移位、瘢痕增生、乳房凹陷程度评分均优于对照组,差异有统计学意义（P＜0.05）; 观察组干预后APGAR评分为（7.35±1.35）分,高于对照组的（5.48±1.39）分,差异有统计学意义（P＜0.05）; 观察组并发症发生率为2.94%,低于对照组的11.76%,差异有统计学意义（P＜0.05）。结论 家属参与模式可降 低乳腺癌患者围术期并发症发生率,提升乳房美观度和家属关怀度。     

预见性护理对乳腺癌整形保乳术患者乳房美观度的影响

目的 观察预见性护理应用于乳腺癌整形保乳术后对患者乳房美观度的影响。方法 选择2022年 5月-2023年2月于我院行乳腺癌整形保乳术的44例患者为研究对象,采用随机数字表法分为对照组和研究 组,每组22例。对照组给予常规护理,研究组给予预见性护理,比较两组乳房美观度、乳房美容效果及心 理状况。结果 研究组乳头纵向移位距离、乳头横向移位距离、乳房凹陷程度、瘢痕增生、乳房对称性评 分均高于对照组（P＜0.05）;研究组乳房美容优良率为90.91%,高于对照组的59.09%（P＜0.05）;研究组 护理后HAMD评分、HAMA评分均低于对照组（P＜0.05）。结论 为乳腺癌整形保乳术后患者提供预见性 护理能有效改善乳房美容度,提升乳房美容效果,有利于调节患者的不良情绪,值得临床应用。     

Detected, yet not Diagnosed - Breast Cancer Screening with MRI Mammography in High-Risk Women

BACKGROUND: MRI has been demonstrated to be the most sensitive imaging method for detecting breast cancer in women at high risk, allowing depiction of cancers that are occult on mammography, ultrasound and clinical breast examination. This high sensitivity is tempered by imperfect specificity due to overlap in the features of benign and malignant lesions. CASE: We present the case of a young BRCA2 mutation carrier whose breast cancer could have been diagnosed 2 years earlier; this is a rare case of a false-negative finding in MRI. DISCUSSION: We discuss morphological, physiological and psychological reasons for underestimation of MRI sets, especially in young women. CONCLUSION: We conclude that double reading in MR screening for breast cancer in high-risk women, as conducted for mammography screening, could be considered.     

Prevention and Management of Lymphedema after Breast Cancer Treatment

Lymphedema of the arm after breast cancer treatment continues to challenge clinicians worldwide. In this review, we examine the main modalities, both nonsurgical and surgical, to prevent and treat this as yet incurable condition.     

乳腺癌改良根治术同期乳房重建的安全性和患者满意度评价

目的观察乳腺癌改良根治术同期行背阔肌肌皮瓣乳房重建的临床效果,评价患者满意度。方法选择病理确诊的乳腺癌患者22例(重建组),行腺癌改良根治术并同期行背阔肌肌皮瓣乳房重建术;匹配同龄、同学历、同TNM肿瘤分期的非乳房重建患者22例作对照(对照组),以Harris标准评价重建乳房的美容效果。随访3年,观察癌组织局部复发转移情况;对患者术后6个月、12个月、24个月和36个月的满意度进行评价。结果两组3年均无肿瘤局部复发及远处转移。乳房重建组优、良、一般分别为14例、5例和3例,患者满意度高于对照组(P0.05),时间因素和分组因素无交互作用(P>0.05)。结论乳腺癌改良根治术同期行背阔肌肌皮瓣乳房重建,不但保证了肿瘤治疗的效果,而且患者的形体美,满意度高。