原发性乳腺癌分子分型与新辅助化疗疗效及预后的相关性

目的 探讨原发性乳腺癌分子分型与新辅助化疗疗效及预后之间的相关性。方法 回顾性分析河南省肿瘤医院收治的204例接受新辅助化疗患者的临床病理资料,分为Luminal A、LuminalB、HER2阳性和三阴乳腺癌4种亚型,分析乳腺癌分子分型对新辅助化疗疗效及预后的预测作用。结果 204例患者中,40例（19.6％）为Luminal A亚型,46例（22.5％）为Luminal B亚型,36例（17.6％）为HER2阳性亚型,82例（40.2％）为三阴乳腺癌亚型。HER2阳性（22.2%）及三阴乳腺癌亚型（22.4%）的病理完全缓解（pCR）率明显高于Luminal A亚型（2.5％）及Luminal B亚型（6.5％）,差异有统计学意义（P=0.03）。与Luminal亚型相比,HER2阳性及三阴乳腺癌亚型具有更差的无病生存期（DFS）（P=0.001）和OS（P=0.002）;剔除获得pCR的患者,单独评价存在肿瘤残留的患者,我们发现HER2阳性及三阴乳腺癌亚型比Luminal亚型具有更差的DFS（P<0.001）和OS（P<0.001）。获得pCR的乳腺癌患者的5年DFS和总生存期（OS）均明显高于化疗后仍有癌残留的患者（P=0.002, P=0.012）。结论 相对于Luminal亚型,HER2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是HER2阳性和三阴乳腺癌亚型预后反而更差。     

三阴性乳腺癌内科治疗现状及展望

三阴性乳腺癌（TNBC）是指雌激素受体（ER）、孕激素受体（PR）及人类表皮生长因子受体2（HER2）均为阴性的乳腺癌。相较于其他亚型的乳腺癌,TNBC是一类高度异质性肿瘤,具有发病年轻、侵袭性强、早期远处转移率高、进展快、预后差的特点,已成为目前乳腺癌研究的热点和难点。本文将对TNBC的内科治疗现状及展望作一综述。     

乳腺癌新辅助化疗联合免疫治疗的临床研究进展

乳腺癌作为一种全身性疾病,单纯依靠手术难以根治,新辅助化疗可以进一步遏制肿瘤发展,增加治疗成功率,并且能够对术后情况进行预测,但是,新辅助化疗联合手术的治疗方案效果仍不理想。为此,迫切需要新的治疗策略和药物来进一步提高乳腺癌患者的生存率。免疫疗法是前沿的抗肿瘤治疗方法,相关研究显示,在新辅助化疗的基础上进行免疫治疗能够有效提高患者的病理学完全缓解率。因此,新辅助化疗联合免疫治疗成为乳腺癌新的治疗选择。三阴性乳腺癌（TNBC）和人表皮生长因子受体2(HER2)阳性乳腺癌是乳腺癌中两种非常特殊的亚型,预后较差。本文对近年来新辅助化疗联合免疫治疗在TNBC及HER2阳性乳腺癌中的临床研究进展进行综述。     

三阴性乳腺癌治疗进展简

三阴性乳腺癌（TNBC）是ER、PR、HER2受体均阴性的乳腺癌,是具有独特的生物学及临床特征的乳腺癌亚型,与基底细胞样乳腺癌有较高的一致性。众所周知ER、PR、HER2的表达是目前临床乳腺癌治疗的靶点,但TNBC患者因为缺少这些靶点,不能从内分泌治疗及靶向治疗中获益,导致了其预后差、复发转移率高、死亡率高,也因此成为近几年乳腺癌研究和关注的焦点。本文旨在对TNBC治疗相关的国内外研究现状做一综述。     

HER2低表达对早期乳腺癌预后的影响分析

摘 要： ［目的］ 比较早期乳腺癌中不同人表皮生长因子受体2(human epidermal growth factor receptor 2，HER2)蛋白表达患者的临床病理特征及预后的差异性。［方法］ 收集2010年6月至2019年6月内蒙古医科大学附属医院甲状腺乳腺外科收治的792例Ⅰ~Ⅱ期乳腺癌患者的临床病理资料，入组患者根据HER2蛋白表达水平分为HER2不表达301例、HER2低表达309例、HER2阳性182例三组，回顾性分析不同HER2亚组患者临床病理特征及预后的差异性。［结果］ HER2低表达患者主要以Luminal A型为主，三阴性乳腺癌（triple-negative breast cancer，TNBC）所占比例较低。与HER2不表达患者相比，HER2低表达患者腋窝淋巴结阳性、脉管癌栓及激素受体（hormone receptor，HR）阳性所占比例较高，浸润性小叶癌、组织学分级以及Ki-67高表达所占比例较低。共随访792例患者，中位随访时间为56个月，HER2阳性、HER2低表达、HER2不表达患者5年无病生存率（disease free survival，DFS）分别为85.7%、92.9%、91.3%（?字2＝8.268，P＝0.016），5年总生存率（overall survival，OS）分别为92.8%、97.4%、96.8%（?字2＝15.809，P<0.001），按HR状态分层分析后5年DFS差异也无统计学意义。［结论］ 虽然HER2低表达乳腺癌具有独特的临床病理特征，但并未导致HER2低表达和HER2不表达乳腺癌预后差异。研究结果支持HER2低表达乳腺癌作为独立的生物学亚型。     

2022年改变晚期乳腺癌临床实践的重要研究

随着乳腺癌综合治疗水平的提高和抗肿瘤药物的不断发展，晚期乳腺癌患者的生存情况有了明显改善。乳腺癌进入精细分类、精确分层的新阶段，2022年晚期乳腺癌研究领域取得了多项突破性进展，各亚型治疗有了新的变化，研究结果影响诊疗指南，改变临床实践。激素受体阳性晚期乳腺癌的研究重点在于细胞周期蛋白依赖性激酶4和6(cyclindependentkinase4and6,CDK4/6)抑制剂治疗失败患者的治疗。人表皮生长因子受体2(humanepidermalgrowthfactor receptor 2,HER2)阳性晚期乳腺癌的治疗中新型抗HER2的抗体药物偶联物（antibody-drug conjugate,ADC）成为研究热点。晚期三阴性乳腺癌（triple-negative breast cancer,TNBC）中免疫治疗需要更多的研究证据，靶向Trop-2的ADC取得了一定疗效。HER2低表达晚期乳腺癌属于特定人群，ADC治疗正在改变临床实践模式。本文对2022年度不同类型晚期乳腺癌的研究进展进行总结，以期更好地指导晚期乳腺癌的治疗，改善患者预后。     

肿瘤干细胞在三阴性乳腺癌治疗耐药中的作用及机制研究进展

三阴性乳腺癌（TNBC）是雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体2（HER-2）蛋白均呈阴性的临床亚型,占所有乳腺癌病例的15%~20%。与其他亚型相比,TNBC更具侵袭性,其预后差、复发转移率和病死率高。一直以来,TNBC的治疗面临着巨大的挑战,由于治疗靶点的缺乏,细胞毒性化疗是唯一被批准用于TNBC的全身治疗方案。为了改善TNBC患者的疗效,研究者们开展了大量的临床试验来探索更多有效的治疗手段。乳腺癌干细胞（BCSC）的自我更新分化是乳腺癌发生发展的重要机制,能够调控乳腺癌的侵袭转移和治疗抵抗,TNBC中肿瘤干细胞（CSC）比例的升高与化疗耐药和不良预后相关。本综述阐述了TNBC的治疗现状以及CSC在TNBC的发生发展、治疗耐药中的作用机制,探讨了CSC及相关信号因子作为TNBC治疗靶点的潜在价值。     

三阴性乳腺癌组织中PD-L1和CD8+ TIL的水平及其临床意义

目的：探讨程序性死亡蛋白-配体 1（programmed death ligand-1,PD-L1）和肿瘤浸润淋巴细胞（tumor-infiltrating lymphocyte, TIL）在三阴性乳腺癌（triple-negative breast cancer,TNBC）组织中的水平及其临床意义。方法：收集2015年1月至 2019年1月福建医科大学附属第二医院手术切除的 61 例 TNBC 患者的癌及癌旁组织石蜡标本,用免疫组化法检测癌组织中 PD-L1表达和CD8+ TIL的水平,用卡方检测方法分析TNBC 组织中PD-L1 和 CD8+ TIL 水平与患者临床病理特征及预后的关 系。结果：PD-L1和CD8+TIL在TNBC组织中的阳性率分别为63.9%（39/61）和32.8%（20/61）。PD-L1表达与TNBC患者的肿瘤 大小、淋巴结转移、病理分期、复发与否有明显关联（均P<0.05）,与患者的年龄、肿瘤分化程度、脉管侵犯以及Ki67表达水平无明 显关联（均P>0.05）;CD8+ TIL水平与TNBC 患者的肿瘤大小、肿瘤分化程度、淋巴结转移、病理分期、复发与否有明显关联 （均P<0.05）,与患者的年龄、脉管侵犯以及Ki67表达水平无明显关联（均P>0.05）。PD-L1和CD8+TIL水平与患者的无进展生存 期（PFS）及总生存期（OS）具有显著相关性（均P<0.05）,PD-L1+ 或者缺乏CD8+ TIL与患者更差的PFS及OS相关（均P<0.05）。结 论：TNBC组织中存在较高水平的PD-L1和CD8+TIL,PD-L1阳性表达或缺乏CD8+TIL与肿瘤侵袭性增加相关,也与患者更差的 PFS及OS相关。     

雄激素受体在三阴性乳腺癌组织中的表达及其与临床病理特征及预后的相关性

目的:检测雄激素受体（AR）在三阴性乳腺癌（TNBC）组织中的表达情况,及其与临床病理特征及预后的相关性。方法:选取2012年至2016年间101例经病理确诊三阴性乳腺癌患者肿瘤组织标本,通过免疫组化法(IHC)检测肿瘤组织雄激素受体（AR）表达状况,分析AR表达与不同临床病理参数及预后的相关性。结果:在101例TNBC患者中,AR表达阳性患者27例(26.7%),AR表达阴性患者74例(73.3%)。AR阳性TNBC较AR阴性TNBC更多表现为非浸润性导管癌（P=0.015）和较低的组织学分级（I/II,P=0.000）及低Ki-67表达(P=0.010)。AR阳性较AR阴性TNBC患者具有较好的无病生存期及总生存期(P=0.014,P=0.021)。单因素回归分析显示,AR阴性表达、高的组织学分级、肿瘤直径大于2 cm与不良的无进展生存期显著相关（P＜0.05）;AR阴性表达、高的组织学分级、肿瘤直径大于2 cm与不良的总生存期显著相关（P＜0.05）。多因素Cox回归分析显示,AR阳性表达为判断TNBC患者良好无进展生存期及良好总生存期的独立因素（P＜0.05）。结论:AR表达与多种临床病理因素存在相关性,AR表达对TNBC患者预后有显著影响,AR可能在三阴性乳腺癌靶向治疗中具有重要作用。     

靶向Trop2的抗体偶联药物治疗三阴性乳腺癌的研究进展

乳腺癌是目前全球发病率最高的恶性肿瘤之一,其中三阴性乳腺癌（triple-negative breast cancer,TNBC）占浸润性乳腺癌的10%～20%。TNBC是一种高度异质性和侵袭性的恶性肿瘤,与其他乳腺癌亚型相比,TNBC治疗手段相对匮乏,预后较差,临床上亟待寻找可用于精准治疗及提高预后的新靶点。人滋养层细胞表面抗原2(trophoblast cell surface antigen 2,Trop2)在三阴性乳腺癌及多种恶性肿瘤中高表达,其通过细胞表面受体信号在肿瘤细胞的增殖、黏附、侵袭、转移中发挥重要作用,以其为靶点的抗体偶联药物（antibody-drug conjugate,ADC）在临床上中具有广阔的应用前景。本文对靶向Trop2的ADC治疗TNBC的临床研究进展予以综述,为靶向Trop2的ADC在TNBC治疗中的临床应用和提高患者生存预后方面提供参考。     

nab-Paclitaxel for the Treatment of Aggressive Metastatic Breast Cancer

Despite advances in early diagnosis, prevention, and treatment, breast cancer remains the second-leading cause of cancer-related deaths in women. The 5-year survival rate for patients with metastatic breast cancer (MBC) is just 24%. However, some forms of MBC appear to be more aggressive than others. Triple-negative breast cancer (TNBC; lacking overexpression of human epidermal growth factor receptor 2 [HER2] and expression of estrogen and progesterone receptors) and breast cancers that overexpress HER2 are the 2 biologically defined subtypes with the worst prognoses. Although a number of effective options have been developed for the treatment of HER2-overexpressing disease, TNBC remains a difficult-to-treat subtype. In addition to hormone receptor and HER2 status, multiple other factors are predictive of relatively poorer clinical outcomes, including visceral metastasis, short disease-free interval between the end of treatment for early-stage disease and diagnosis of MBC, and higher number of metastatic sites. There is an urgent need to improve therapy for patients with aggressive forms of breast cancer. Taxanes are considered among the most active classes of compounds against breast cancer. This review specifically examines the clinical trials in which nab-paclitaxel was used to treat patients with MBC and factors associated with poor prognosis.     

Differential response of triple‐negative breast cancer to a docetaxel and carboplatin‐based neoadjuvant treatment

BACKGROUND:

In this study, the authors evaluated whether a pathologic complete response (pCR) or a clinical complete response (cCR) to neoadjuvant treatment in patients with locally advanced breast cancer differed among the 3 subtypes of breast cancer: triple‐negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, and hormone receptor‐positive/HER2‐negative breast cancer. Whether a cCR or a pCR was correlated with fewer recurrences and better survival also was investigated.

METHODS:

Patients with stage II/III breast cancer received 4 cycles of neoadjuvant docetaxel and carboplatin (TC) every 3 weeks. Patients with HER2‐positive tumors were randomized to receive either additional weekly trastuzumab preoperatively or TC alone. Postoperatively, all patients received 4 cycles of TC, and all HER2‐positive patients received a total of 52 weeks of trastuzumab. The recurrence‐free survival (RFS) and overall survival (OS) rates at 2 years were reported.

RESULTS:

Seventy‐four patients were enrolled, including 11 patients with TNBC, 30 patients with HER2‐positive tumors, and 33 patients with hormone receptor‐positive/HER2‐negative tumor. The cCR rates were 45.4%, 50% and 40.6% in TNBC, HER2‐positive, and hormone receptor‐positive/HER2‐negative groups, respectively. The pCR rate for the entire group was 26.8%, and patients with TNBC had the best response (54.6%) followed by patients with HER2‐positive tumors (24.1%) and patients with hormone receptor‐positive/HER2‐negative tumors (19.4%; P = .0126). The pCR rate for patients with HER2‐positive tumors improved from 7% to 40% if trastuzumab was added (P = .08). Infiltrating ductal cancer, TNBC, negative estrogen receptor and/or progesterone receptor status, tumor classification predicted a pCR (P ≤ .05). Multivariate analysis using a logistic regression test indicated that tumor type was an independent predictor. The RFS rate for patients who did versus patients who did not achieve a pCR was 93.8% versus 78.4% at 2 years, respectively, and 83.3% versus 58% at 3 years, respectively (P = .1227); whereas, for patients who did versus patients who did not achieve a cCR, the RFS rate was 80.9% versus 83.9%, respectively, at 2 years and 65% versus 64.3%, respectively, at 3 years (P = .999).

CONCLUSIONS:

The current results indicated that the TC combination is promising for the treatment of TNBC. The addition of trastuzumab to TC improved the pCR rate significantly in patients with HER2‐positive breast cancer. Cancer 2010. © 2010 American Cancer Society.     

Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer

The purpose of the present study was to identify histological surrogate predictive markers of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). Among 474 patients who received NAC and subsequent surgical therapy for stage II?CIII invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens obtained before NAC were available. As controls, CNB specimens from 42 tumors of the hormone receptor-negative and HER2-positive (HR?/HER2+) subtype and 46 tumors of the hormone receptor-positive and HER2-negative (HR+/HER2?) subtype were also included. Histopathological examination including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis, and immunohistochemical studies for basal markers were performed, and the correlation of these data with pathological therapeutic effect was analyzed. The rates of pCR at the primary site were higher for TNBC (32%) and the HR?/HER2+ subtype (21%) than for the HR+/HER2? subtype (7%) (P?=?0.006). Expression of basal markers and p53, histological grade 3, high TIL scores, and apoptosis were more frequent in TNBC and the HR?/HER2+ subtype than in the HR+/HER2? subtype (P?=?0.002 for TIL and P?<?0.001 for others). In TNBC, the pCR rates of tumors showing a high TIL score and of those showing a high apoptosis score were 37 and 47%, respectively, and significantly higher or tended to be higher than those of the tumors showing a low TIL score and of the tumors showing a low apoptosis score (16 and 27%, respectively, P?=?0.05 and 0.10). In a total of 180 breast cancers, the pCR rates of the tumors showing a high TIL score (34%) and of those showing a high apoptosis score (35%) were significantly higher than those of the tumors showing a low TIL score (10%) and those of the tumors showing a low apoptosis score (19%) (P?=?0.0001 and 0.04, respectively). Histological grade and basal marker expression were not correlated with pCR. Although the whole analysis was exploratory, the degree of TIL correlated with immune response appear to play a substantial role in the response to NAC in TNBC.     

Breast cancer-specific survival by clinical subtype after 7 years follow-up of young and elderly women in a nationwide cohort

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20–89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70–89) more often had luminal A-like tumors. Compared to age 50–59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81–2.82), while elderly had two to five times higher mortality rate (70–79: HR = 2.25, 1.87–2.71; 80–89: HR = 5.19, 4.21–6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.     

分子分型在乳腺癌辅助治疗选择中的临床研究

目的:探讨分子分型与乳腺癌患者临床特征的关系,分析分子分型在乳腺癌辅助治疗中的临床疗效以及安全性。方法:选择2011年4月至2014年5月来我院诊治的109例乳腺癌患者,回顾性分析临床资料,按照ER、PR和HER2的表达情况分成4种分子亚型,探讨分子分型与乳腺癌患者临床特征的关系,不同分子分型乳腺癌患者采取不同的治疗方案。同期选择20例乳腺癌组成对照组患者,采取常规化疗方案治疗,分析各组治疗的临床疗效以及安全性。结果:在109例乳腺癌患者中,分子分型各型所占例数分别为:Luminal A型50例（45.87%）、Luminal B型20例（18.35%）、HER2阳性型22例（20.18%）、三阴型17例（15.60%）。四种分子亚型在绝经前后占据的患者例数、原发肿瘤各期所占例数以及除II期以外的临床分期所占例数均存在明显差异性,具有统计学意义（P<0.05）。在年龄、组织学类型、临床分期方面四种分子亚型所占的例数无明显差异性（P>0.05）。不同治疗方案下,Luminal A型、Luminal B型、HER2阳性型以及三阴型乳腺癌患者的总缓解率分别为86.0%、80.0%、81.8%和70.6%,均显著高于对照组患者30.0%的总缓解率,具有明显差异性（P<0.05%）。109例乳腺癌患者的完全缓解率为80.7%,16例SD患者中,6例为Luminal A型患者,3例为Luminal B型患者,3例为HER2阳性型患者,4例为三阴型患者。经过检测,三种治疗方案均发生粒细胞减少、肝脏毒性、消化道毒性、外周神经毒性、脱发以及其他并发症。其中三种治疗方案发生粒细胞减少、消化道毒性与外周神经毒性等并发症的例数存在差异性（P<0.05）。所有患者只需减少药量,不良反应均可减轻甚至消除。结论:乳腺癌患者分为Luminal A型、Luminal B型、HER2阳性型以及三阴型四种分子亚型,比例最高的是Luminal A型。不同的分子亚型采取不同的治疗方案,能够获得令人满意的治疗效果,但会发生一些较轻的不良反应。分子分型对乳腺癌患者的治疗具有重要的指导作用,值得在临床上推广。     

Clinicopathological features and treatment strategy for triple-negative breast cancer

Breast cancers are divided into at least 4 subtypes on the basis of gene expression profiles and expression of receptors (hormone receptors (HR) and HER2) as measured by immunohistochemistry. These subtypes have different prognoses and responses to treatments such as endocrine manipulation, anti-HER2 therapy, and chemotherapy. Triple-negative breast cancer (TNBC) is immunohistochemically defined as lacking estrogen and progesterone receptors and not overexpressing HER2. TNBC accounts for approximately 15% of breast cancer patients, and is more chemosensitive but has a worse prognosis than the HR-positive/HER2-negative phenotype. TNBC is a heterogeneous disease that does not offer specific targets in the same way as HR-positive and HER2-positive breast cancers, and is similar to basal-like breast cancer and BRCA1-related breast cancer. At present, the lack of highly effective therapeutic targets for TNBC leaves standard chemotherapy, for example the combination of anthracycline and taxane, as the only medical treatment, but this is insufficiently efficacious. Novel approaches for TNBC, for example DNA damaging agents, PARP-1 inhibitors, receptor tyrosin kinase inhibitors (TKIs), and antiangiogenesis agents, have been examined in clinical settings. Concerning therapeutic strategies for TNBC, it is most important to develop novel effective approaches for TNBC treatment and high-throughput predictive tools for standard chemotherapy and novel agents.     

Treatment of triple negative breast cancer (TNBC): current options and future perspectives

Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led to the identification of 4 major breast cancer "intrinsic" subtypes, including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive and basal-like breast cancer (BLBC). These subtypes have distinct phenotypes, molecular profiles, clinical behaviour and response to therapy, with the BLBC carrying the worst outcome. Microarray analysis is not feasible in routine practice and therefore oncologists rely on a simpler immunohistochemical (IHC) classification to identify relevant breast cancer subtypes. Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression at IHC analysis. TNBC is strictly related to BLBC and, given the lack of common therapeutic targets, represent a major challenge for breast oncologist. In this review we will summarize the updated knowledge on TNBC, with emphasis on its current treatment and on the new therapeutic options under development.     

Early-stage Triple-negative Breast Cancer: Time to Optimize Personalized Strategies

Triple-negative breast cancer (TNBC) accounts for approximately 15%-20% of breast cancers diagnosed worldwide, which amounts to almost 200 000 cases each year. Although historically TNBC is considered difficult to treat with a poor prognosis, there is emerging evidence showing excellent response rates in a subset of TNBC patients. Attempts to de-escalate chemotherapy in hormone-receptor-positive (HR+) and HER2-neu amplified breast cancer subtypes have been successful. At present, robust strategies to personalize therapy in early-stage TNBC do not exist, and despite excellent response rates in a subset of patients, all patients are exposed to the same several cycles of cytotoxic chemotherapy. Personalizing therapy in TNBC represents a challenge due to the scarcity of treatment options outside of cytotoxic chemotherapy and limited predictive and prognostic biomarkers to tailor treatment. Recent developments in understanding TNBC biology have sparked interest in exploring treatment optimization and personalization with the goal of achieving excellent response rates and long-term clinical outcomes, while simultaneously reducing physical, psychological, and financial toxicities for select patients. Here, we provide an update on the current evidence to support future studies examining de-escalating chemotherapy in patients with low-risk TNBC and adjuvant intensification strategies to improve outcomes for patients who are at high risk for systemic failure despite current standard-of-care treatments.     

Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases

PurposeEvaluation of the influence of immunohistochemically defined breast cancer (BC) subtypes and other risk factors on the development of cerebral metastases (CM).MethodsExploratory analysis of a hospital-based prospective tumour registry including all patients with primary BC treated in our EUSOMA breast unit between 1998 and 2006.ResultsThe study cohort contained 2441 patients, including 284 patients (11.6%) with triple-negative (oestrogen receptor (ER), progesterone receptor (PR) and HER2-negative) and 245 patients (10.1%) with HER2-overexpressing BC subtypes. Overall, 80 patients (3.3%) developed CM within a median follow-up period of 47 months, 19 (23.8%) of them with triple-negative and 19 (23.8%) with HER2-positive tumours. Therefore, 6.7% of all patients with triple-negative and 7.8% of patients with HER2-positive breast cancer developed CM. Multivariate analysis indicated that the highest risk for CM was triple-negative breast cancer. Further independent risk factors were: HER2-overexpression, early onset BC (age < 50 years), and large tumour size (pT3/4). Among those patients developing CM, triple-negative BC showed the shortest interval between primary diagnosis and occurrence of CM with a median of 22 months, compared to 30 and 63.5 months in HER2-positive and ER+/HER2- BC, respectively. Survival after occurrence of CM did not differ among the subtypes.ConclusionPatients with triple-negative or HER2-positive BC have a higher risk for CM compared with patients bearing the ER+/HER2- phenotype and develop CM earlier in the course of disease. A risk profile for CM might help adjust surveillance in high risk populations and identify patients with a need for new treatment strategies.     

Association of Immunohistochemically Defined Molecular Subtypes with Clinical Response to Presurgical Chemotherapy in Patients with Advanced Breast Cancer

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with differentclinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive andnot available in the developing countries where the majority of patients present at advanced stage. The St GallenConsensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR,HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosedpatients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtypewith the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the thirdcycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like andHER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively.Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer(TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed byHER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity wasobserved within each subgroup, being most marked in the TNBC although the most responding tumors, 8%developing clinical-progressive-disease. The study supports association of molecular subtypes with response tochemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.