Trastuzumab (Herceptin®) improves disease-free survival (DFS) and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess ...the magnitude of its clinical benefit for subpopulations defined by nodal and steroid hormone receptor status using data from the Herceptin Adjuvant (HERA) study.
HERA is an international multicenter randomized trial comparing 1 or 2 years of trastuzumab treatment with observation after standard chemotherapy in women with HER2-positive breast cancer. In total, 1703 women randomized to 1-year trastuzumab and 1698 women randomized to observation were included in these analyses. Median follow-up was 23.5 months. The primary endpoint was DFS.
The overall hazard ratio (HR) for trastuzumab versus observation was 0.64 95% confidence interval (CI) 0.54–0.76; P < 0.0001, ranging from 0.46 to 0.82 for subgroups. Estimated improvement in 3-year DFS in subgroups ranged from +11.3% to +0.6%. Patients with the best prognosis (those with node-negative disease and tumors 1.1–2.0 cm) had benefit similar to the overall cohort (HR 0.53, 95% CI 0.26–1.07; 3-year DFS improvement +4.6%, 95% CI -4.0% to 13.2%).
Adjuvant trastuzumab therapy reduces the risk of relapse similarly across subgroups defined by nodal status and steroid hormone receptor status, even those at relatively low risk for relapse.
Background: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens ...for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. Patients and methods: Patients with stage T2–T4 primary breast cancer were scheduled to receive 6–8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5–14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 μg/kg/day or lenograstim 150 μg/m2/day) on days 5–10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). Results: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. Conclusion: Ciprofloxacin alone, or daily G-CSF from day 5–10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin.
Zusammenfassung
Die endokrine Therapie gehört zu den wirkungsvollsten zielgerichteten Therapiemaßnahmen in der adjuvanten Behandlung des Mammakarzinoms. Die Therapiedauer beträgt in der initialen ...adjuvanten Therapie (IAT) 5 Jahre, sie kann bei adäquatem Rückfallrisiko durch die erweiterte endokrine Therapie (EAT) um weitere 5 Jahre (Jahr 6–10) verlängert werden. Patientinnen mit positivem Hormonrezeptorstatus (ER Östrogenrezeptor und/oder PR Progesteronrezeptor) des Primärtumors sollten eine endokrine Therapie erhalten. In der Prämenopause stellt eine 5‑jährige Behandlung mit Tamoxifen (bei Kontraindikation gegen Tamoxifen ersetzt durch ein GnRHa „gonadotropin releasing hormone analogues“) den Therapiestandard dar. Nur bei einem erhöhten Rückfallrisiko, bei bestehender Ovarialfunktion, einem Alter unter 35 Jahren und nach einer adjuvanten Chemotherapie sollten Tamoxifen bzw. bei Kontraindikation gegen Tamoxifen ein Aromatasehemmer (AI) in Kombination mit GnRHa gegeben werden. Bei postmenopausalen Patientinnen kann die Therapie entweder mit einem AI über 5 Jahre (besonders bei high-risk Patientinnen und Patientinnen mit einem lobulären invasiven Mammakarzinom, dann für 5 Jahre) begonnen werden, alternativ kann eine klassische oder inverse Sequenztherapie mit Tamoxifen und AI durchgeführt werden. Die EAT kann mit Tamoxifen, oder beim Eintritt der Menopause, mit einem AI für 2–5 Jahre ergänzt werden. Ist eine adjuvante Chemotherapie indiziert, so erfolgt die adjuvante endokrine Therapie nach Abschluss der Chemotherapie. Grundsätzlich kann die endokrine Therapie gleichzeitig mit der Strahlentherapie der Brust erfolgen.
Summary It is well documented that the aromatase inhibitors (AIs) are superior to tamoxifen as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer. ...However, compared with tamoxifen, an elevated incidence of arthralgia has been observed during AI treatment. Concerns have been raised that AI-induced arthralgia may dissuade patients from completing their full AI treatment course, and may also deter physicians from prescribing an AI if they feel that patients may be at risk of permanent joint damage. Patient education about the possibility of experiencing arthralgia, and effective management of symptoms if they appear, are important in helping patients adhere to AI treatment, and consequently improving breast cancer outcomes. In this paper, we discuss the potential mechanisms behind AI-induced arthralgia, review the frequency with which arthralgia occurs, and propose for the first time an algorithm specifically for the treatment of AI-induced arthralgia. As with joint pain in non-breast cancer patients, a sequential approach to disease management is recommended, involving modifying the patient’s lifestyle in addition to taking a stratified approach to pharmacological intervention with analgesia and anti-inflammatory medication. Knowing that joint symptoms can be managed in most patients may encourage patient–physician communication and treatment compliance.
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