When art imitates life
James Fleck & Fernando Souza: Anticancerweb v1 Nov 29th, 2018
The International Agency for Cancer Research (IARC) has just launched the Global Cancer Observatory 2018, updating the international epidemiological data from 185 countries. Despite the expected population heterogeneity, the use of ASR (age-standardized rate) allowed the identification that breast cancer is the leading malignant tumor in incidence (ASR = 46.3) and mortality (ASR = 13.0) in the world. Around 20% of these breast cancer patients would express Her-2 gene amplification, which would require a more specific treatment.
By the turn of the 21st century, Dr. Dennis Slamon, chief of the division of Hematology-Oncology at UCLA initiated the era of breast cancer customized treatment. He identified Her-2 receptor as a biological target for breast cancer treatment with a monoclonal antibody called trastuzumab. At the beginning, Dr. Slamon had no idea of the magnitude of his work, immortalized in the movie "Living Proof." The video shows "Living Proof" inspiration behind the scenes. Trastuzumab was responsible for an important impact on the palliative and curative breast cancer treatment, affecting quantitatively and qualitatively the lives of thousands of women. More recently, another monoclonal antibody called pertuzumab has been developed. This, by preventing Her-2 receptor dimerization, interferes with signal transduction via PI3K and MAPK, promoting a synergistic effect with trastuzumab.
In 2015, the New England Journal of Medicine published the final analysis of the study "Clinical Evaluation of Pertuzumab and Trastuzumab" (CLEOPATRA) after a median follow-up of 50 months. A total of 808 patients with locally or metastatically relapsed Her-2 positive breast cancer cells were accrued. Patients were randomized to a test arm containing the combination pertuzumab + trastuzumab + docetaxel or a control arm composed of placebo + trastuzumab + docetaxel combination. It consisted of an intention-to-treat (ITT) blinded phase III study. The primary endpoint was overall survival, with a median of 56 months in the test arm and 40.8 months in the control arm (HR 0.68 p <0.001). There was a crossover in 48 patients of the control arm, which made the results more reliable. The increase of 15.7 months in overall survival supported a new standard, however, the spectrum of potential predictive factors remained undefined.
The dual anti-Her2 therapy has also been proposed in the curative (adjuvant) treatment of high-risk patients (axillary node + or primary tumor larger than 2 cm). The APHINITY trial published in the New England Journal of Medicine in July 2017 showed an improvement at three-year invasive disease-free survival when pertuzumab was added to trastuzumab in the adjuvant treatment of high-risk Her2 positive breast cancer patients.
Science will continue to make history searching for more sophisticated and customized treatments.
Medicine will continue to translate science rational and methodological thinking into effective physician’s artistic interventions.
Medicine will continue to combine technical knowledge with patient’s emotional values based on physician’s perception.
Medicine is an aesthetic creative process both inspiring and imitating art.
Sandra M. Swain, José Baselga, Sung-Bae Kim, et al: Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer, New Engl J Med 372: 724 – 734, 2015
Gunter von Minckwitz, Marion Procter, Evandro de Azambuja, et al: Adjuvant Pertuzumab and Trastuzumab inEarly HER2- Positive Breast Cancer,New Engl J Med377:122-131, 2017
Dr. Dennis Slamon's Inspiration Behind "Living Proof" - Stand up to Cancer: You tube link: https://www.youtube.com/watch?gl=SN&hl=fr&threaded=1&v=vsa7oTsYaEE, Jul 13th, 2010