Medical Oncology News in Breast Cancer 2014

Abstract

Recent studies have shown the significant clinical advances made in the treatment of breast cancer patients with human epidermal growth factor receptor-2-positive (HER2+) disease over the past 15 years. According to a meta-analysis conducted among HER2+ breast cancer patients who received the adjuvant trastuzumab therapy (including the HERA trial, the NCCTG N9831 trial, the NSABP B-31 trial, the PACS 04 trial and the FinHER trial), the therapy increased both the disease-free survival (DFS) and overall survival (OS) rates among patients with tumours ≤ 2 cm, while also contributed to favourable outcomes previously reported for patients with hormone receptor–positive (HR+) tumours ≤ 2 cm and 0-1 positive lymph node.

The ALTTO trial that compared the sequential and concurrent uses of lapatinib and trastuzumab treatments for early stage HER2+ breast cancer patients indicated that lapatinib was associated with significant increase in adverse events (AEs) of special interest like diarrhea, hepatobiliary, and rash or erythema compared to trastuzumab alone but made no significant difference in 4-year DFS or OS. Meanwhile, the Text and Soft trial compared two types of hormonal therapy: tamoxifen with ovarian function suppression (OFS) and exemestane (EXE) with OFS. It found that EXE + OFS significantly improved DFS, breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) and it could serve as another treatment option for postmenopausal women diagnosed with early HR+ breast cancer.

Another study, Bolero-2, looked at patients with estrogen-receptor-positive (ER+) and human epidermal growth factor receptor-2-negative (HER2-) locally advanced or metastatic breast cancer whose condition recurred or progressed after receiving nonsteroidal aromatase inhibitor (NSAI) treatment. The subjects were divided into two groups and treated with either everolimus (EVE) (10 mg/day) and EXE (25 mg/day), or placebo (PBO) + EXE (25mg/day). The results showed that the period of progression-free survival (PFS) prolongation was clinically meaningful and statistically significant (median 4.6-month benefit; P < .0001) among the subjects, but the secondary endpoint of OS did not reach statistical significance (P = .14). In the Optimize-2 study, which aimed at examining the frequency of continued zoledronic acid for breast cancer patients with bone metastases after they received therapy with ≥ 9 doses of intravenous bisphosphonate (BP). Results showed that continuing zoledronic acid treatment at a reduced dosing frequency of every 12 weeks was noninferior to those with a dosing frequency of every 4 weeks (noninferiority margin: 10%).

Separately, a study conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) concluded that obesity was independently associated with breast-cancer-related mortality in premenopausal patients with ER+ breast cancer. However, obesity had no significant effect in premenopausal women with ER-negative disease or among postmenopausal women. Weight loss had a favourable effect on inflammatory and metabolic biomarkers.

All studies are propelling the development of medical oncology forward for the sake of patients’ benefits. However, physicians should consider every individual factor when designing a treatment plan. The findings from various studies would be valuable references for the process of medical treatment.

近年，不少研究顯示第二型人類上皮生長因子受體呈陽性(HER2+)的乳癌患者的臨床治療技術，於過去 15 年來都有明顯的進步。當中有一項整合研究針對接受曲妥珠單抗靶向治療(trastuzumab therapy)(包括 HERA 試驗, NCCTG N9831 試驗,NSABP B-31 試驗, PACS 04 試驗 和 FinHER 試驗)的 HER2+乳癌患者，結果顯示曲妥珠單抗靶向治療有助於提升腫瘤大小兩厘米或以下患者的無病生存率(disease-free survival)和總生存率(overall survival)，而對那些腫瘤大小兩厘米或以下而激素受體呈陽性(hormone receptor–positive)及淋巴結呈陽性 (positive lymph node)的患者也有顯著效果。

另一項試驗名為 ALTTO trial，旨在研究 HER2+的早期乳癌患者在先後或一起接受拉帕替尼(lapatinib)與曲妥珠單抗兩種靶向治療藥物的效果，發現有接受拉帕替尼的組別，她們短期內產生的不良反應（腹瀉、肝膽管毛病及皮疹或紅斑）會較高，但兩組的 4 年期無病生存率和總生存率均沒有明顯差異。與此同時，Text and Soft 試驗將兩組患者進行比較，一組服用三苯氧胺(tamoxifen)與抑制卵巢功能(ovarian function suppression)，另一組則服用依西美坦(exemestane)與抑制卵巢功能，結果顯示服用依西美坦與抑制卵巢功能的無病生存率，無乳癌期(breast cancer-free interval)和遠端無復發生存期(distant recurrence-free interval) 均有顯著的提升。這可為激素受體呈陽性的早期及已收經的乳癌患者提供多一個治療的選擇。

Bolero-2 試驗研究將接受非類固醇芳香環轉化酶抑制劑(nonsteroidal aromatase inhibitor)的雌激素受體(estrogen receptor)呈陽性及第二型人類上皮生長因子受體(HER-2)呈陰性的晚期乳癌患者，分兩組服用癌伏妥(everolimus)( 每天 10 毫克)和依西美坦(每天 25 毫克)或安慰劑(placebo)和依西美坦(每天 25 毫克)，結果表示無惡化存活期(progression-free survival)延長了 4.6 個月(中位數)(P < .0001)，但總生存率卻沒有顯著差異(P = .14)。而在 Optimize-2 的研究中，主要探討確診有骨轉移的乳癌患者在接受 9 次或以上的雙磷酸鹽類藥物(bisphosphonate)後延續不同次數的唑來磷酸治療(zoledronic acid treatment)的效果，結果顯示接受減少劑量（每 12個星期一次）的唑來磷酸治療的患者，不會比每 4 個星期接受一次劑量的患者為差，非劣性差異值(noninferiority margin)為 10%。

Early Breast Cancer Trialists’ Collaborative Group(EBCTCG)也發表了一項研究報告，當中提及肥胖對於尚未收經的雌激素受體呈陽性 (estrogen receptor-positive)的乳癌患者的乳癌相關死亡率(breast-cancer-related mortality)是有關連的，但對於尚未收經的雌激素受體呈陰性或已收經的患者，肥胖卻不是影響因素。另外，減重則有助於改善炎症(inflammatory)及代謝的生物標誌物(metabolic biomarkers)。 持續的研究能推動內科腫瘤醫學的發展，讓整體患者受惠。不過，醫護人員在制定治療方案時，他們除了參考研究結果，也需要將每位患者的自身因素也考慮在內。