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Turning scientific serendipity into discoveries in breast cancer research and treatment: a tale of PhD students and a 50-year roaming tamoxifen team.

ABSTRACT:

Purpose

This retrospective, about a single "mobile" laboratory in six locations on two continents, is intended as a case study in discovery for trainees and junior faculty in the medical sciences. Your knowledge of your topic is necessary to expect the unexpected.

Historical method

In 1972, there was no tamoxifen, only ICI 46, 474, a non-steroidal anti-estrogen with little chance of clinical development. No one would ever be foolish enough to predict that the medicine, 20 years later, would achieve legendary status as the first targeted treatment for breast cancer, and millions of women would benefit from long-term adjuvant tamoxifen therapy. The secret of tamoxifen's success was a translational research strategy proposed in the mid 1970's. This strategy was to treat only patients with estrogen receptor (ER)-positive breast cancer and deploy 5 or more years of adjuvant tamoxifen therapy to prevent recurrence. Additionally, tamoxifen prevented mammary cancer in animals. Could the medicine prevent breast cancer in women?

Results

Tamoxifen and the failed breast cancer drug raloxifene became the first selective estrogen receptor modulators (SERMs): a new drug group, discovered at the University of Wisconsin, Comprehensive Cancer Center. Serendipity can play a fundamental role in discovery, but there must be a rigorous preparation for the investigator to appreciate the possibility of a pending discovery. This article follows the unanticipated discoveries when PhD students "get the wrong answer." The secret of success of my six Tamoxifen Teams was their technical excellence to create models, to decipher mechanisms, that drove the development of new medicines. Discoveries are listed that either changed women's health or allowed an understanding of originally opaque mechanisms of action of potential therapies. These advances in women's health were supported entirely by government-sponsored peer-reviewed funding and major philanthropy from the Lynn Sage Breast Cancer Foundation, the Avon Foundation, and the Susan G. Komen Breast Cancer Foundation. The resulting lives saved or extended, families aided in a time of crisis and the injection of billions of dollars into national economies by drug development, is proof of the value of Federal or philanthropic investment into unencumbered research aimed at saving millions of lives.

SUBMITTER: Jordan VC

PROVIDER: S-EPMC8557169 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction PhD is the highest awarded degree offered by universities in different disciplines. Owners of a PhD can teach at universities, start independent research and receive a higher salary while further building a scientific career. We examined whether the publication output before the PhD degree has a correlation with subsequent research activities. Methods We downloaded publication and citation data from the Hungarian Scientific Bibliography for Hungarian researchers who obtained PhD between the ages of 24 and 45. The researchers were grouped into eleven scientific sections. We examined the number of Q1 publications published in the previous 5 years, the H-index, the total number of citations for the last complete year, and the biological age of the researcher. Each parameter was computed for the year at which the PhD was obtained and ten years later. Pre-PhD publications (and citations for these) were excluded when assessing post-PhD track records. Spearman rank correlation and Kruskal-Wallis test were computed. Results We analyzed all together 4,790 researchers. We obtained a positive correlation between the number of Q1 publications before and after PhD (corr. coeff. = 0.21–0.54, p<0.01 in all sections), between the H-index before and after PhD (corr. coeff. = 0.32–0.56, p<0.01 in all sections), and between the citations received before and after PhD (corr. coeff. = 0.34–0.51, p<0.01 in all sections). All three metrics measured ten years after the PhD were negatively correlated with the age of the researcher at the time of obtaining the PhD (number of publications corr. coeff. = -0.09–0.22, p<0.05; H-index corr. coeff. = -0.09–0.29, p<0.08; number of citations corr. coeff. = -0.14–0.30, p<0.01). Among all disciplines, Philosophy and History and Engineering sciences show the strongest correlation between pre- and post-PhD output. When running multiple regression analysis for all three metrics as dependent variables and the number of articles, the H-index, the number of citations in the year of the PhD, the calendar year of PhD, and the gender of the researcher as independent variables, the number of articles and the H-index in the year of PhD reached the strongest positive correlations while gender had a negative correlation. Conclusions We independently evaluated pre- and post-PhD publication performance. In connection with age, the discipline-specific reference values of scientometric parameters at the time of obtaining the PhD can help to select candidates for postdoctoral grants and positions.