A Phase II Prospective, Randomized, Double-Blind, Placebo-Controlled and Multicenter Clinical Trial to Assess the Safety of 0.005% Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women with Early Stage Breast Cancer in Treatment with Aromatase Inhibitor in the Adjuvant Setting.

LESSONS LEARNED: The levels of circulating follicle-stimulating hormone, luteinizing hormone, estriol, estradiol, and estrone remained unchanged after a 12-week treatment with 0.005% estriol vaginal gel in postmenopausal women receiving nonsteroidal aromatase inhibitors for hormone receptor-positive early breast cancer. These results support the safety of 0.005% estriol vaginal gel for the treatment of bothering symptoms of vulvovaginal atrophy in breast cancer survivors. The results provide clinicians with confidence in the use of this product in women who do not experience symptom relief with nonhormonal remedies. BACKGROUND: Symptoms of vulvovaginal atrophy associated with treatment with nonsteroidal aromatase inhibitors (NSAIs) negatively impact patients' quality of life and may affect adherence to NSAIs. Vaginal estrogens effectively improve these symptoms, although their safe use in breast cancer survivors remains unclear. METHODS: Postmenopausal women with hormone receptor-positive early breast cancer receiving NSAI and moderate-to-severe vaginal dryness were randomized to 0.005% estriol vaginal gel or placebo for 12 weeks. Circulating estrogens, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed at baseline and at weeks 1, 3, 8, and 12. The primary safety outcome was the variation in serum FSH from baseline to week 12. RESULTS: Sixty-one women (mean age, 59 years) enrolled in the study. Small oscillations were observed in FSH and LH, although they were always maintained within the postmenopausal range. No significant differences were found in the variation of FSH and LH between baseline and week 12 from the physiological variation observed before treatment. Women receiving 0.005% estriol vaginal gel had slightly increased estriol levels at weeks 1 and 3, with a subsequent reduction until normalizing at week 12; estradiol and estrone remained the below limit-of-quantitation in almost all samples. CONCLUSION: Ultralow-dose 0.005% estriol vaginal gel did not significantly influence estrogens, FSH, and LH levels in women with breast cancer receiving NSAI. A transient negligible absorption of estriol and a nonsignificant variation of FSH after 12 weeks were observed. These findings provide confidence for the safe use of 0.005% estriol vaginal gel in women with breast cancer with an indication for treatment with vaginal estrogens.

The economic burden of metastatic breast cancer in Spain.

Objectives: The study aimed to estimate the burden of metastatic breast cancer (mBC) in Spain over 5 years. Methods: An incidence-based cost-of-illness model was developed in which a cohort of patients with mBC was followed from the diagnosis of metastatic disease over 5 years or death. Resource use data were collected through a physician survey conducted with 10 clinical experts in Spain. The model distinguished patients according to HER2 and hormonal receptor (HR) status, and followed the patient cohort in monthly cycles. Results: The incident cohort was estimated to be 2,923 patients with mBC, consisting of 1,575 HER2-/HR+, 520 HER2+/HR+, 324 HER2+/HR-, and 503 triple negative patients. The estimated mean survival over the 5-year time period was 2.51 years, on average, with longer survival of 3.36 years for HER2+/HR+, 2.41 years for HER2-/HR+, 2.82 years for HER2+/HR- and shortest mean survival of 1.74 years for triple negative patients. The total costs were €469,92,731 for the overall population, €190,079,787 for the HER2-/HR+, €151,045,260 for the HER2+/HR+, €80,827,171 for the HER2+/HR- and €47,540,512 for the triple negative subgroups over 5 years. Per patient total costs were €160,642 on average, €120,664 for HER2-/HR+, €290,346 for HER2+/HR+, €249,152 for HER2+/HR-and €94,572 for triple negative patients over 5 years. Conclusions: The economic burden of mBC in Spain is significant, but differs by HER2 and HR status. HER2-/HR +patients account for the highest burden due to the prevalence of this category, but HER2+/HR +patients have the highest per patient costs.

Trastuzumab subcutáneo: revisión de los datos clínicos y de preferencia / Subcutaneous trastuzumab: a review of the clinical and preference data

El cáncer de mama HER2 positivo supone aproximadamente un 15% de los tumores malignos de mama. La terapia anti-HER2, principalmente representada por trastuzumab, es el pilar del tratamiento de esta enfermedad. La prolongación en la supervivencia que han conseguido las nuevas terapias anti-HER2, y el tratamiento dilatado de estas pacientes en los estadios precoces de la enfermedad así como en la enfermedad avanzada, supone un importante reto a los recursos existentes, tanto con respecto al personal sanitario y el tiempo de los hospitales de día oncológicos, como en cuanto al tiempo dedicado por las pacientes para su tratamiento. El desarrollo de una formulación subcutánea ha supuesto una disminución significativa en la utilización de estos recursos y facilidad de uso. En esta revisión, presentamos el desarrollo de esta nueva formulación, así como los datos de eficacia y preferencia (AU)

HER2-positive breast cancer accounts for approximately 15% of all malignant breast tumors. HER2-targeted therapy, mainly trastuzumab, remains the cornerstone of treatment. The increase in survival achieved by the new anti-HER2 therapies, and the prolonged treatment of these patients, both in the early and advanced breast cancer setting, poses a major challenge to existing health resources. This challenge involves the health personnel, the time consumed by oncologic day hospitals, and the time investment required by patients. The development of the new trastuzumab subcutaneous formulation has improved optimization of health resources and has increased ease of use. In the present article, we review the development of the drug, as well as efficacy and preference data (AU)

Cáncer de mama y embarazo. Análisis de una serie de 27 pacientes / Breast cancer and pregnancy. Analysis of a series of 27 patients

Objetivo: Realizar un análisis descriptivo de la serie de pacientes con cáncer de mama (CM) y embarazo diagnosticadas en nuestro centro en relación con los métodos terapéuticos empleados y supervivencia global de la serie. Pacientes y métodos: Entre 1982 y 2009, de 5.906 pacientes diagnosticadas de CM, se trató a 27 pacientes con CM y embarazo (0,46%). Analizamos las características clínicas y anatomopatológicas, el diagnóstico, los tratamientos y la evolución de estas pacientes en nuestro centro. Resultados: La edad media al diagnóstico fue de 35 años. Durante la gestación se diagnosticó a 21 pacientes y en el posparto, a 6. El retraso medio diagnóstico desde el inicio de los síntomas fue de 4 meses. Respecto al perfil inmunohistoquímico determinado en 19 pacientes, 5 (26%) eran receptor 2 de factor de crecimiento epidérmico humano (HER2) positivo; otros 5 (26%), triple negativo; 3, luminal A, y en las 6 restantes, luminal B. Al diagnóstico, se clasificó a 5, 9, 11 y 2 pacientes en estadio I, II, III y IV, respectivamente. Histológicamente, 21 (78%) eran carcinomas ductales infiltrantes; 11 (41%), de alto grado histológico, y 4 casos (15%) presentaron características de carcinoma tipo inflamatorio al diagnóstico. Se pautó quimioterapia neoadyuvante en 16 pacientes (59%), sin que se detectaran complicaciones fetales. Se operó a todas las pacientes, y se realizó mastectomía radical modificada en 24 (89%), así como cirugía conservadora en 3. Con un tiempo medio de seguimiento de 60 meses, la supervivencia global fue del 70%. Cuatro pacientes (15%) presentaron recaída local y 13 (48%), recaída sistémica. Conclusiones: El carcinoma de mama durante el embarazo se asocia con un retraso diagnóstico, estadios avanzados y grados histológicos altos. El tratamiento quirúrgico conlleva un alto porcentaje de mastectomías radicales. La quimioterapia no produjo efectos adversos en el feto tras el primer trimestre de gestación. El pronóstico de CM durante el embarazo es similar al de las pacientes no gestantes de la misma edad y estadio tumoral (AU)

Objective: To perform a descriptive analysis of patients with breast cancer (BC) and pregnancy diagnosed in our centre, as regards the therapeutic methods used and the overall survival of the series. Patients and methods: Between 1982-2009, 5906 patients were diagnosed with BC, of whom 27 (0.46%) were treated for pregnancy-associated BC. We analysed the characteristics, diagnosis, treatments and outcome of these patients in our centre. Results: The mean age at diagnosis was 35 years. Twenty-one patients were diagnosed during pregnancy and six of them in the post-partum period. The mean diagnostic delay from the onset of symptoms was four months. In the immunohistochemical profile performed in 19 patients, 5 (26%) were HER2, 5 (26%) were triple-negative, luminal A in three patients, and luminal B in the other 6 cases. At diagnosis, 5, 9, 11 and 2 patients were classified into stages I, II, III and IV, respectively. Histologically, 21 (78%) were infiltrating ductal carcinomas, 11 (41%) were high grade carcinomas and 4 (15%) were inflammatory carcinomas at diagnosis. Neoadjuvant chemotherapy was prescribed in 16 patients (59%), with no foetal complications detected. All patients underwent surgery; 24 (89%) had modified radical mastectomy while three had conservative surgery. The mean follow-up time was 60 months, in which the overall survival was 70%. Four patients (15%) had local recurrence and 13 (48%) had systemic recurrence. Conclusions: Breast carcinoma during pregnancy is associated with diagnostic delay, advanced stages and high histological grades. Surgical treatment involves a high percentage of radical mastectomies. Chemotherapy did not produce adverse effects in the foetus after the first trimester. The prognosis for BC during pregnancy is similar to that of non-pregnant patients of the same age and tumour stage(AU)