Experiences and Perceptions of Older Adults with Lower-Risk Hormone Receptor-Positive Breast Cancer about Adjuvant Radiotherapy and Endocrine Therapy: A Patient Survey

Older patients with lower-risk hormone receptor-positive (HR+) breast cancer are frequently offered both radiotherapy (RT) and endocrine therapy (ET) after breast-conserving surgery (BCS). A survey was performed to assess older patients’ experiences and perceptions regarding RT and ET, and participation interest in de-escalation trials. Of the 130 patients approached, 102 eligible patients completed the survey (response rate 78%). The median age of respondents was 74 (interquartile range 71–76). Most participants (71%, 72/102) received both RT and ET. Patients felt the role of RT and ET, respectively, was to: reduce ipsilateral tumor recurrence (91%, 90/99 and 62%, 61/99) and improve survival (56%, 55/99 and 49%, 49/99). More patients had significant concerns regarding ET (66%, 65/99) than RT (39%, 37/95). When asked which treatment had the most negative effect on their quality of life, the results showed: ET (35%, 25/72), RT (14%, 10/72) or both (8%, 6/72). Participants would rather receive RT (57%, 41/72) than ET (43%, 31/72). Forty-four percent (44/100) of respondents were either, “not comfortable” or “not interested” in participating in potential de-escalation trials. Although most of the adjuvant therapy de-escalation trials evaluate the omission of RT, de-escalation studies of ET are warranted and patient centered.     

Adherence to Adjuvant Endocrine Therapy in Christchurch Women with Early Breast Cancer

Aims

To assess adherence to adjuvant endocrine therapy by a real-world cohort of women in Christchurch and to determine any associated factors.

乳腺癌内分泌治疗耐药的研究进展

乳腺癌内分泌治疗作为乳腺癌综合治疗的方法之一,具有不可替代的重要性.然而,内分泌治疗的疗效因其耐药性受到限制.文章旨在对乳腺癌内分泌治疗耐药的机制及逆转耐药的治疗进展进行综述,为临床内分泌治疗提供新的方向.     

Factors Associated with “Survivor Identity” in Men with Breast Cancer

Cancer patients vary in their comfort with the label “survivor”. Here, we explore how comfortable males with breast cancer (BC) are about accepting the label cancer “survivor”. Separate univariate logistic regressions were performed to assess whether time since diagnosis, age, treatment status, and cancer stage were associated with comfort with the “survivor” label. Of the 70 males treated for BC who participated in the study, 58% moderately-to-strongly liked the term “survivor”, 26% were neutral, and 16% moderately-to-strongly disliked the term. Of the factors we explored, only a longer time since diagnosis was significantly associated with the men endorsing a survivor identity (OR = 1.02, p = 0.05). We discuss how our findings compare with literature reports on the comfort with the label “survivor” for women with BC and men with prostate cancer. Unlike males with prostate cancer, males with BC identify as “survivors” in line with women with BC. This suggests that survivor identity is more influenced by disease type and treatments received than with sex/gender identities.     

Gynecologic Symptoms among Hormone Receptor-Positive Breast Cancer Patients on Oral Endocrine Therapy: A Cross-Sectional Study

Endocrine therapy (ET) for hormone receptor-positive (HR+) breast cancer can contribute to gynecologic symptoms (GS) that impact vaginal health, sexual function, and quality of life (QoL). A cross-sectional study was conducted at St. Michael’s Hospital in Toronto, Canada between July 2017 and June 2018 to examine the occurrence and frequency of GS among HR+ breast cancer patients on ET, patient-provider communication, female sexual dysfunction (FSD), and QoL. A Treatment Experience questionnaire was developed for this study and the Female Sexual Function Index (FSFI) and Menopause-Specific Quality of Life questionnaire (MENQOL) were also administered. Of 151 patients surveyed, 77 (51.0%) were on tamoxifen and 74 (49.0%) on an aromatase inhibitor. Most patients (84.1%, 95% confidence interval [CI] 77.3% to 89.5%) experienced at least one GS “all the time” or “often”, or one or more infections, in the past year. Only 44 (31.9%) patients reported that their oncologist had ever previously asked them about experiencing GS. The prevalence of FSD was 61.2% (95% CI 46.2% to 74.8%) among 49 sexually active patients that completed the FSFI. Symptoms captured in the MENQOL’s vasomotor domain were deemed most bothersome. Side effect management and patient-provider communication should be prioritized to optimize GS, vaginal health, and sexual function of ET users.     

激素受体阳性晚期乳腺癌的内分泌治疗进展

内分泌耐药是激素受体阳性晚期乳腺癌的治疗难题之一.根据耐药机制,内分泌治疗引入靶向药物有望逆转或延迟耐药,并已在临床研究中取得验证.寻找分子标志物,选择获益人群,是这个领域发展的重要方向.     

Responsiveness to endocrine manipulations in breast cancer after “prophylactic” castration

Two hundred and one cases of premenopausal women with breast cancer who underwent prophylactic castration with subsequent recurrence were reviewed to ascertain the degree of responsiveness of these patients to subsequent endocrine manipulation. We show that the standard endocrine manipulations, particularly the major ablations, retain a fair degree of activity in this group. There is a suggestion that the longer the castration-recurrence interval, the higher the chance of a response, but the difference is significant only for osseous-dominant disease. As in other patient groups, responders to subsequent endocrine manipulations live longer than nonresponders.     

The “Sandwich” Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate–High- and High-Risk Endometrial Cancer

(1) Background: In intermediate–high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The “sandwich” schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the “sandwich” schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate–high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin–paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The “sandwich” schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate–high- and high-risk EC.     

来曲唑与三苯氧胺在绝经后期乳腺癌新辅助内分泌治疗中的疗效对比

目的 比较来曲唑与三苯氧胺用于绝经后期乳腺癌新辅助内分泌治疗的近期疗效和毒副反应.方法将收治的绝经后期、ER阳性、有合并症的55例乳腺癌随机分为两组,并行新辅助内分泌治疗.来曲唑组25例:2.5 mg/次,1次/d,连续60 ～90 d;三苯氧胺组30例:10mg/次,2次/d,连续60～90 d.比较两组的近期疗效和...     

Appraising Adjuvant Endocrine Therapy in Hormone Receptor Positive HER2-Negative Breast Cancer—A Literature Review

Background: Approximately 75% of breast cancer (BC) is associated with luminal differentiation expressing endocrine receptors (ER). For ER+ HER2− tumors, adjuvant endocrine therapy (ET) is the cornerstone treatment. Although relapse events steadily continue, the ET benefits translate to dramatically lengthen life expectancy with bearable side-effects. This review of ER+ HER2− female BC outlines suitable adjuvant treatment strategies to help guide clinical decision making around appropriate therapy. Methods: A literature search was conducted in Embase, Medline, and the Cochrane Libraries, using ER+ HER−, ET BC keywords. Results: In low-risk patients: five years of ET is the standard option. While Tamoxifen remains the preferred selection for premenopausal women, AI is the choice for postmenopausal patients. In the high-risk category: ET plus/minus OFS with two years of Abemaciclib is recommended. Although extended ET for a total of ten years is an alternative, the optimal AI duration is undetermined; nevertheless an additional two to three years beyond the initial five years may be sufficient. In this postmenopausal group, bisphosphonate is endorsed. Conclusions: Classifying the risk category assists in deciding the treatment route and its optimal duration. Tailoring the breadth of ET hinges on a wide array of factors to be appraised for each individualized case, including weighing its benefits and harms.     

唑来膦酸在乳腺癌辅助治疗中的临床应用及机制探讨

第三代双膦酸盐类药物唑来膦酸是治疗乳腺癌骨转移公认的标准药物之一,但其在乳腺癌辅助治疗中的应用地位尚存在争议。目前临床研究结果表明,唑来膦酸辅助治疗不仅可以提高骨密度．而且可以降低乳腺癌的复发和转移。在低雌激素水平环境下,唑来膦酸可使早期乳腺癌患者得到生存获益．而且早期应用的益处优于延迟应用。唑来膦酸通过抑制肿瘤转移过程中的多条途径而发挥抗肿瘤作用。但唑来膦酸的最佳剂量、治疗周期及持续时间尚有待进一步的研究予以确认。     

来曲唑在老年乳腺癌新辅助内分泌治疗中的疗效观察

目的探讨来曲唑在老年绝经后乳腺癌新辅助内分泌治疗中的近期疗效,耐受性及与临床病理因素的相关性。方法对58例绝经后激素受体阳性的乳腺癌患者进行来曲唑新辅助内分泌治疗,以他莫昔芬新辅助内分泌治疗为对照组。结果来曲唑组临床疗效显著优于他莫昔芬组（P〈0.05）。来曲唑组临床分期晚,ER及PR均阳性的有效率高,与HER-2表达无关。他莫昔芬组HER-2阳性的有效率低。2组治疗前后Ki-67水平均显著下降,有统计学意义（P〈0.05）。2组未出现明显不良反应。结论绝经后、激素受体阳性的乳腺癌选择来曲唑新辅助内分泌治疗安全,有效,尤其适合有合并症的老年体弱者。     

Management Strategies for Older Patients with Low-Risk Early-Stage Breast Cancer: A Physician Survey

When managing older patients with lower-risk hormone-receptor-positive (HR+), HER2 negative (HER2−) early-stage breast cancer (EBC), the harms and benefits of adjuvant therapies should be taken into consideration. A survey was conducted among Canadian oncologists on the definitions of “low risk” and “older”, practice patterns, and future trial designs. We contacted 254 physicians and 21% completed the survey (50/242). Most respondents (68%, 34/50) agreed with the definition of “low risk” HR+/HER2− EBC being node-negative and either: ≤3 cm and low histological grade, ≤2 cm and intermediate grade, or ≤1 cm and high grade. The most popular chronological and biological age definition for older patients was ≥70 (45%, 22/49; 45% 21/47). In patients ≥ 70 with low risk EBC, most radiation and medical oncologists would recommend post-lumpectomy radiotherapy (RT) and endocrine therapy (ET). Seventy-eight percent (38/49) felt that trials are needed to evaluate RT and ET’s role in patients ≥ 70. The favored design was ET alone, vs. RT plus ET (39%, 15/38). The preferred primary and secondary endpoints were disease-free survival and quality of life, respectively. Although oncologists recommended both RT and ET, there is interest in performing de-escalation trials in patients ≥ 70.     

Full Compliance of Adjuvant Endocrine Therapy Is Associated with Higher Disease-Free Survival in Hormone Receptor-Positive and HER2-Negative Chinese Breast Cancer Patients with First Tumor Recurrence

Purpose: To characterize the compliance status of adjuvant endocrine therapy (aET) and its relationship with disease-free survival (DFS) in hormone receptor-positive (HR+) and HER2-negative (HER2−) in Chinese breast cancer (BC) patients with first tumor recurrence. Methods: All women with primary unilateral stage I – III HR+HER2− BC and first tumor recurrence in 2008 - 2018 at our institution were identified. Full (vs. none/partial) compliance of aET was classified from records. Multivariate Cox regression estimated the hazard ratio (HR), its 95% confidence interval (CI), and p value. DFS. Covariates included age, T stage, N stage, pathology, tumor grade, LVI, chemotherapy, radiotherapy.      Results: A total 258 patients had average age 47.4 years at BC diagnosis and median DFS 31.7 months. Patients with ipsilateral (contralateral) region and organ recurrence were 47.7% (19.8%) and 71.9%. Compared to the patients with none/partial compliance of aET, the full compliance patients (54.3% ) had a higher DFS (median 35.0 vs. 25.2 months, p=0.009). Multivariate analysis showed that the full compliance of aET was associated with a lower HR 0.614 (95%CI 0.467 – 0.807, p<0.001) on recurrence. Early discontinuation (67.5%, 56/83) due to the drug side effects was the top reason for partial compliance of aET. Conclusions: Full compliance of aET was quite low in Chinese HR+HER2− BC patients. However, it was associated with a 38.6% lower risk of first tumor recurrence. To search for effective tools to improve the compliance of aET in this population should be stressed.     

Adjuvant Endocrine Therapy of Perimenopausal and Recently Postmenopausal Women With Hormone Receptor-Positive Breast Cancer

Although 5 years of tamoxifen has been the standard adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer for more than 2 decades, emerging results suggest that either switching to an aromatase inhibitor after 5 years of tamoxifen when postmenopausal or continuing tamoxifen for an additional 5 years can further decrease relapse risk. As a result, more premenopausal breast cancer patients will be continuing adjuvant endocrine therapy through the menopause transition. In this setting, questions arise regarding continued tamoxifen use through 10 years and/or the timing and appropriateness of switching to an aromatase inhibitor. In addition, it is now recognized that estrogen levels substantially decline for approximately 2 years after the last menstrual period and that chemotherapy and/or tamoxifen-induced amenorrhea preclude reliable ovarian function determination. Because aromatase inhibitors are only effective in a low estrogen environment without ovarian estrogen production, determination of the optimal endocrine adjuvant therapy for perimenopausal women and those recently postmenopausal represent a challenge requiring understanding of current clinical study results and the potential for interactions among therapeutic interventions, ovarian function, and clinical outcome. Available options include tamoxifen for 10 years, tamoxifen for 5 years followed by aromatase inhibitors, tamoxifen with a luteinizing hormone-releasing hormone (LHRH) agonist, aromatase inhibitor with an LHRH agonist or aromatase inhibitor with bilateral oophorectomy. Although completed (Austrian Breast Cancer Study Group [ABCSG]-12) and ongoing (SOFT [Suppression of Ovarian Function Trial], TEXT [Tamoxifen and Exemestane Trial]) clinical trials are addressing some issues, many questions will remain requiring individualized clinical judgement. Rationale supporting the available endocrine therapy options in this setting and recommendations for clinical management follow.     

Initiation of Adjuvant Endocrine Therapy in Black and White Women With Breast Cancer

Background

Adjuvant endocrine therapy reduces risk of recurrence and mortality in women with hormone receptor–positive breast cancer, yet many women never initiate it. We examined the influence of race, sociocultural factors, and process-of-care factors on initiation of adjuvant endocrine therapy in a racially diverse sample.

Metastatic Breast Cancer: Therapeutic Options According to Molecular Subtypes and Prior Adjuvant Therapy

In spite of advances in treatment strategies, about 25%–40% of patients with breast cancer still eventually develop metastatic disease that is largely incurable. Treatment goals vary from symptom control to lengthening survival, mainly on the basis of patient age and performance status, tumor biology, site and extent of disease, and prior therapies. In particular, breast cancer molecular characterization allows for the identification of breast cancer subtypes with distinct biological features, a distinct clinical course, and distinct treatment sensitivity. Endocrine manipulation is the cornerstone of therapy in hormone receptor–positive tumors; anti–human epidermal growth factor receptor (HER)‐2 agents are essential in the management of HER‐2⁺ tumors; and chemotherapy is the only available option so far for the triple‐negative subtype. In each of these subtypes, the more efficacious agents have been progressively incorporated into adjuvant treatment. As a consequence, the choice of the optimal therapeutic strategy for patients with metastatic disease is largely influenced by prior exposure to adjuvant therapies. This review contextualizes the data from clinical trials into different clinical scenarios of metastatic disease, taking into account the molecular subtype and prior adjuvant treatments.