虽然老年乳腺癌患者大约占全部乳腺癌患者的三分之一，但是70岁以上患者（尤其伴有合并症时）通常被临床研究排除在外。尽管70岁以下患者对化疗的获益似乎与年龄基本无关，然而70岁以上患者化疗获益的可靠数据仍然很少。过度治疗被认为有害，可降低生活质量、浪费资源和破坏环境，对于70岁以上雌激素受体阳性HER2阴性乳腺浸润癌女性患者，这些风险尤其重要，术后除了标准的内分泌治疗，化疗的作用仍有争议。对于老年患者，日益虚弱的体力和越来越多的合并症，可加重治疗副作用对生活质量的影响，而非癌症相关死亡风险越来越高，抗癌治疗改善总生存的可能性微乎其微。尤其雌激素受体阳性HER2阴性乳腺癌与其他乳腺癌相比，往往复发于术后数十年，可能超过老年患者的寿命。那么，对于高风险乳腺癌年龄≥70岁患者，术后要不要化疗？

　　2025年7月31日，国际四大医学期刊之首、创刊于1823年的英国《柳叶刀》正刊发表法国综合癌症中心联盟老年肿瘤学组和乳腺学组ASTER 70s研究报告，首次根据预后基因组特征，对高风险乳腺癌年龄≥70岁患者术后内分泌治疗±化疗的总生存进行随机比较。

  • ASTER 70s (NCT01564056): Adjuvant Systemic Treatment for (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment

  • Official Title: Adjuvant Systemic Treatment for Oestrogen-receptor (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment. A French UNICANCER Geriatric Oncology Group (GERICO) and Breast Group (UCBG) Multicentre Phase III Trial

　　该多中心三期随机对照优效研究于2012年4月12日至2016年4月14日在法国和比利时84个临床中心，入组年龄≥70岁（年龄中位75.1岁，四分位72.5至78.7岁）雌激素受体阳性HER2阴性原发或孤立局部复发乳腺癌完成手术后尚未全身治疗女性患者1969例。首先，在中心实验室采用逆转录聚合酶链反应检测石蜡包埋肿瘤组织8个预后基因，进行基因组分级指数筛查。随后，根据基因组分级指数，将其中1089例高风险乳腺癌患者按1比1随机分为两组：化疗组541例，给予4个周期术后紫杉类或蒽环类化疗，每3周1次，随后进行内分泌治疗；非化疗组548例，仅仅给予内分泌治疗。根据G8筛查工具对老年衰弱、淋巴结状态和中心评分，对随机分组进行分层，其中437例（40%）患者G8评分≤14，被诊断为老年衰弱。主要终点为总生存，目前仍在积极随访。

　　结果，中位随访7.8年（95%置信区间：7.5～7.8），化疗组与非化疗组相比：

  • 4年总生存率：90.5%比89.3%（95%置信区间：87.6～92.8、86.2～91.6）绝对值相差1.3个百分点（95%置信区间：-2.4～5.0）

  • 8年总生存率：72.7%比68.3%（95%置信区间：67.8～77.0、63.3～72.7）绝对值相差4.5个百分点（95%置信区间：-2.1～11.1）

  • 总死亡风险比：0.83（95%置信区间：0.63～1.11，分层对数秩P=0.2100，无统计学意义）

　　安全性分析结果表明，出现至少1次≥3级不良事件：

  • 非化疗组：52例（9%，包括1例治疗无关死亡）

  • 化疗组：183例（34%，包括3例死亡，其中1例治疗相关死亡）

　　因此，该研究结果表明，即使对于基因组分级指数高风险雌激素受体阳性HER2阴性乳腺癌≥70岁女性，术后内分泌治疗±术后化疗相比，总生存率并未显著提高，不良事件发生率反而显著提高超过3倍，这为权衡该老年人群术后内分泌治疗±术后化疗的获益与风险提供了重要数据。

　　对此，荷兰癌症研究院肿瘤内科和分子病理专家、乌得勒支大学医学中心病理专家发表同期评论：权衡老年乳腺癌患者的生存质量与数量。

Lancet. 2025 Jul 31;406(10502):489-500. IF: 88.5

Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial.

古稀高风险乳腺癌术后要不要化疗

Etienne Brain, Olivier Mir, Emmanuelle Bourbouloux, Olivier Rigal, Jean-Marc Ferrero, Sylvie Kirscher, Djelila Allouache, Véronique D’Hondt, Aude-Marie Savoye, Xavier Durando, Francois P Duhoux, Laurence Venat-Bouvet, Emmanuel Blot, Jean-Luc Canon, Florence Rollot-Trad, Hervé Bonnefoi, Telma Roque, Jérome Lemonnier, Aurélien Latouche, Julie Henriques, Magali Lacroix-Triki, Dewi Vernerey; GERICO&UCBG/Unicancer.

Institut Curie – Hopital René Huguenin, SAINT-CLOUD, FRANCE; Gustave Roussy Cancer Campus Grand Paris, VILLEJUIF, FRANCE; Institut de Cancérologie de l’Ouest – René Gauducheau, NANTES SAINT HERBLAIN, FRANCE; Centre Antoine Lacassagne, NICE, FRANCE; Centre Henri Becquerel, ROUEN, FRANCE; Institut Sainte Catherine, AVIGNON, FRANCE; Centre Francois Baclesse, CAEN, FRANCE; Institut de cancérologie de L’Ouest – Paul Papin, ANGERS, FRANCE; Institut Curie – Hopital Claudius Regaud, PARIS, FRANCE; Institut régional du Cancer Montpellier Val d’Aurelle, MONTPELLIER, FRANCE; Centre Jean Perrin, CLERMONT-FERRAND, FRANCE; Institut Jean Godinot, REIMS, FRANCE; Cliniques universitaires Saint-Luc, BRUXELLES, BELGIUM; CHU de Limoges, LIMOGES, FRANCE; CHI de Créteil, CRETEIL, FRANCE; CH Bretagne Atlantique, VANNES, FRANCE; Centre Georges-Francois Leclerc, DIJON, FRANCE; Centre Léon Bérard, LYON, FRANCE; Grand Hopital de Charleroi, CHARLEROI, BELGIUM; Centre Oscar Lambret, LILLE, FRANCE; Institut Claudius Regaud, TOUJOUSE, FRANCE; Centre Eugène Marquis, RENNES, FRANCE; Groupement Hospitalier Public du Sud de l’Oise, SENLIS, FRANCE; Institut de Cancérologie de Lorraine VANDOEUVRE LES, NANCY, FRANCE; CHD de Vendée LA, ROCHE-SUR-YON, FRANCE; CHI de Toulon – Hopital Sainte Musse, TOULON, FRANCE; Institut Bergonié, BORDEAUX, FRANCE; CHU de Brest, BREST, FRANCE; Polyclinique Urbain V, AVIGNON, FRANCE; Hopitaux du Léman, THONON-LES-BAINS, FRANCE; Centre Hospitalier René Dubos, CERGY-PONTOISE, FRANCE; Clinique Victor Hugo LE, MANS, FRANCE; Clinique Mutualiste de l’Estuaire, SAINT-NAZAIRE, FRANCE; Institut Paoli-Calmettes, MARSEILLE, FRANCE; Institut de Cancérologie Lucien Neuwirth SAINT PRIEST EN, JAREZ, FRANCE; Centre Paul Strauss, STRASBOURG, FRANCE; Centre Saint-Yves, VANNES, FRANCE; Centre Hospitalier Annecy Genevois, PRINGY CEDEX, FRANCE; Centre Hospitalier Lyon Sud, PIERRE-BENITE, FRANCE; CH du Mans LE, MANS, FRANCE; CHP Saint Grégoire SAINT, GREGOIRE, FRANCE; Centre Hospitalier Alpes Leman CONTAMINE SUR, ARVE, FRANCE; CHR d’Orléans ORLEANS LA, SOURCE, FRANCE; Groupe Hospitalier Paris St Joseph, PARIS, FRANCE; Hopital INDC entité Jolimontoise, JOLIMONT, BELGIUM; Hopital Henri Mondor, CRETEIL, FRANCE; CHI Poissy Saint Germain SAINT GERMAIN EN, LAYE, FRANCE; Clinique Sainte Marguerite, HYERES, FRANCE; Clinique Mathilde, ROUEN, FRANCE; Clinique et Maternité Sainte-Elisabeth, NAMUR, BELGIUM; CHC Saint-Joseph, LIEGE, BELGIUM; Clinique Claude Bernard, ALBI, FRANCE; Clinique du Sud Luxembourg, VIRTON, BELGIUM; CHPLT Verviers, VERVIERS, BELGIUM; CH de Cholet, CHOLET, FRANCE; CH Layné MONT DE, MARSAN, FRANCE; CHA LIBRAMONT, LIBRAMONT, BELGIUM; Hopitaux Universitaires de Strasbourg – Hopital Civil, STRASBOURG, FRANCE; Cliniques Saint-Pierre, OTTIGNIES, BELGIUM; CH de Rodez, RODEZ, FRANCE; Hopital Antoine Béclère, CLAMART, FRANCE; CHU Mont-Godinne, YVOIR, BELGIUM; Clinique Saint Jean du Languedoc, TOULOUSE, FRANCE; CLINIQUE PASTEUR, TOULOUSE, FRANCE; Polyclinique de Francheville, PERIGUEUX, FRANCE; CHU de Poitiers, POITIERS Cedex, FRANCE; Hopital Avicenne, BOBIGNY, FRANCE; Centre Hospitalier Intercommunal de Meulan – Les Mureaux, MEULAN, FRANCE; CHU Ambroise Paré BOULOGNE, BILLANCOURT, FRANCE; Institut Curie, Saint-Cloud, France; Institut Curie, Paris, France; Gustave Roussy, University of Paris Saclay, Villejuif, France; Institut de Cancérologie de l’Ouest, Saint-Herblain, France; Centre Henri Becquerel, Rouen, France; Centre Antoine Lacassagne, Nice, France; Institut Sainte Catherine, Avignon, France; Centre Francois Baclesse, Caen, France; Institut du Cancer de Montpellier, Montpellier, France; Institut Jean Godinot, Reims, France; Centre Jean Perrin, Clermont-Ferrand, France; Cliniques Universitaires Saint-Luc, Brussels, Belgium; CHU Dupuytren, Limoges, France; CH Bretagne Atlantique & ELSAN, Hopital Privé Océane/Centre Saint-Yves, Vannes, France; Grand Hopital de Charleroi, Charleroi, Belgium; Institut Bergonié, Université de Bordeaux UFR Sciences Médicales, Bordeaux, France; Unicancer R&D, Paris, France; Conservatoire National des Arts et Métiers, Paris, France; Centre Hospitalier Universitaire de Besancon, Besancon, France; Université Marie et Louis Pasteur, Besancon, France; Institut Universitaire de Cancérologie de Toulouse-Oncopole, Toulouse, France.

BACKGROUND: For women aged 70 years or older with oestrogen receptor-positive HER2-negative invasive breast cancer, hormonotherapy is a standard adjuvant treatment, while the role of chemotherapy is debated. We aimed to assess the effect of adjuvant chemotherapy on overall survival in these older patients with high-risk tumours according to a prognostic genomic signature.

METHODS: This phase 3, randomised, superiority study was conducted at 84 clinical sites in France and Belgium in women aged 70 years and older with oestrogen receptor-positive and HER2-negative primary breast cancer or isolated local recurrence before any systemic treatment and after complete surgery. Genomic grade index (GGI) testing was done with a reverse-transcriptase PCR assay of eight genes on paraffin-embedded tumour tissue in a central laboratory. Patients with a GGI high-risk tumour were randomly allocated (1:1) to receive either four cycles of postoperative taxane-based or anthracycline-based chemotherapy given every 3 weeks followed by hormonotherapy (chemotherapy group) or hormonotherapy alone (no chemotherapy group). Randomisation was stratified according to the G8 screening tool score for geriatric frailty, nodal status, and centre. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01564056) and is under active follow-up.

FINDINGS: Between April 12, 2012 and April 14, 2016, 1969 patients were screened for GGI, of whom 1089 had a GGI high-risk tumour and were randomly allocated to the chemotherapy group (n=541) or the no chemotherapy group (n=548). Median age was 75.1 years (IQR 72.5 to 78.7) and geriatric frailty (G8 score ≤14) was identified in 437 patients (40%) patients. With a median follow-up time of 7.8 years (95% CI 7.5 to 7.8), overall survival rates were 90.5% (95% CI 87.6 to 92.8) at 4 years and 72.7% (67.8 to 77.0) at 8 years in the chemotherapy group, and 89.3% (86.2 to 91.6) at 4 years and 68.3% (63.3 to 72.7) at 8 years in the no chemotherapy group (stratified log-rank p=0.2100; hazard ratio 0.83 [95% CI 0.63 to 1.11]), yielding statistically non-significant absolute differences in survival probability of 1.3 percentage points (95% CI -2.4 to 5.0) at 4 years and 4.5% (95% CI -2.1 to 11.1) at 8 years. Safety analysis favoured the no chemotherapy group: at least one grade 3 or higher adverse event occurred in 52 (9%) of 548 patients in the no chemotherapy group (including one death not related to treatment), compared with 183 (34%) of 541 patients in the chemotherapy group (including three deaths, of which one was related to treatment).

INTERPRETATION: The addition of adjuvant chemotherapy to hormonotherapy conferred no survival benefit in women aged 70 years and above with a GGI high-risk oestrogen receptor-positive HER2-negative breast cancer, and was associated with more adverse events, providing important data on the benefit-risk balance of adding adjuvant chemotherapy to adjuvant hormonotherapy in this older age group.

FUNDING: Programme Hospitalier de Recherche Clinique (PHRC National Cancer 2011), Cephalon, Amgen, Ipsogen, Association d’Aide à la Recherche Cancérologique de Saint-Cloud, and Ligue Contre le Cancer.

DOI: 10.1016/S0140-6736(25)00832-3

Lancet. 2025 Jul 31;406(10502):422-424. IF: 88.5

Balancing quality and quantity of life in older patients with breast cancer.

Sabine C Linn, Florentine S Hilbers.

Netherlands Cancer Institute, Amsterdam, Netherlands; University Medical Centre Utrecht, Utrecht, Netherlands.

Overtreatment is considered harmful in terms of decreasing quality of life, wasting resources, and environmental damage. These risks are especially relevant when considering adjuvant chemotherapy besides adjuvant endocrine therapy for older adult patients (older than 70 years) with oestrogen receptor-positive, HER2-negative breast cancer. Older patients with breast cancer represent around a third of all patients with breast cancer. However, patients older than 70 years with breast cancer, especially those with comorbidities, have generally been excluded from clinical trials. Although chemotherapy benefit seems to be largely independent of age up to at least 70 years, solid data on chemotherapy benefit in older patients are still scarce. For older patients, increasing frailty and comorbidities influence how side-effects affect their quality of life, while the potential for therapies to improve overall survival is small due to an increased risk of non-cancer-related mortality. This is especially true for oestrogen receptor-positive, HER2-negative breast cancer, in which disease recurrences tend to occur later than for other breast cancer subtypes.

DOI: 10.1016/S0140-6736(25)01233-4