Understanding breast cancer - The long and winding road

Abstract

Background: Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an "excess of black bile" and treatment options including the use of opium and castor oil, prevailed. Surgical resection was introduced in the 18th century. The advent of modern medicine led to the development of novel treatment options that include hormonal, targeted and chemo-therapies. There are still several therapeutic challenges including the treatment of triple negative breast cancer (TNBC), and overcoming drug resistance.

Scope of review: The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. But, mankind has come a long way. Herein, I have traced how our understanding of breast cancer has evolved from the early description of the disease around 460 BCE as "black bile-containing crab-like tumors" to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients. How is breast cancer treated today and how do risk factors, breast cancer subtype and drug resistance contribute to the therapeutic challenges at the turn of the 21st century?

Major conclusions: Breast cancer remains a serious public health issue worldwide. However, appreciable growth in our understanding of breast cancer in the past century has led to remarkable progress in the early detection, treatment and prevention of the disease. The clinical focus is shifting more towards tailored therapy as more targets are characterized and novel highly innovative approaches are developed.

General significance: Tracing the history of breast cancer, highlights how increased awareness of the disease, and progress in research and development have enhance our understanding of the disease.

Keywords: Angelina Jolie; Aromatase inhibitors; BRCA1 and BRCA2; Breast cancer; ER; HER2; Herceptin; Hippocrates; Mammography; Radical mastectomy; Tamoxifen; Triple negative breast cancer (TNBC).

Fig. 1

Timeline: The evolution of breast cancer: 3000 BCE to 2016.

Fig. 2

The Edwin Smith Papyrus: a) Case 39 of the original in hieratic. b) The corresponding modern scientific transcription into hieroglyphics. The images were cropped from the original publication by Breasted. They contain descriptions of tumors with prominent heads in the breast of the patient as transliterated in Harding's publication in 2007. (Harding, F. J. Breast Cancer: Cause, Prevention, Cure. Tekline Publishing, 440 (2007)).

Fig. 3

The mastectomy instrument of Gerard Tabor described in 1721: Image adapted from Cotlar, A. M., Dubose, J. J. & Rose, D. M. History of surgery for breast cancer: radical to the sublime. Curr Surg60, 329–337, doi:10.1016/S0149–7944(02)00777-8 (2003).

Fig. 4

Cancer and breast cancer pioneers: 400 CE – 1900. a) Hippocrates (engraving by Peter Paul Rubens, 1638https://en.wikipedia.org/wiki/Hippocrates); b) Galen (Source: http://famousbiologists.org/galen/); c) René Descartes (Source: Hammond, N. (2006). Descartes - The life of Rene Descartes and its place in his times. Tls-Times Lit Suppl, 27–27); d) Bernardino Ramazzini (source: http://www.britannica.com/biography/Bernardino-Ramazzini); e) Henri François Le Dran (source: https://pictures.royalsociety.org/image-rs-10246); f) Johannes Peter Müller (source: http://www.britannica.com/biography/Johannes-Peter-Muller); g) William Stewart Halsted (source: Rutkow, I.M. (2000). William Stewart Halsted - Moments in surgical history. Arch Surg-Chicago 135, 1478–1478.); h) George Thomas Beatson (image from Wellcome Library, London; Photograph by T. & R. Annan & Son; http://wellcomeimages.org/indexplus/page/Home.html).

Fig. 5

Cancer and breast cancer pioneers: 20th century. a) Wilhelm Conrad Röntgen (source: http://www.britannica.com/biography/Wilhelm-Rontgen); b) Geoffrey Keynes (Source: http://www.modern-humanities.info/people/Keynes_Geoffrey.htm); c) Janet Elizabeth Lane-Claypon (source: http://www.centenary.mrc.ac.uk/news/tales-from-the-century-janet-lane-claypon-and-epidemiology/); d) Robert Egan. (source: http://onlinelibrary.wiley.com/, in the transcript of an interview titled Mammography and Diseases of the Breast); e) Bernard Fisher (Source: http://drbarronlerner.com/, in an article titled: Bernard Fisher's Battle Against the Radical Mastectomy).

Fig. 6

Breast cancer advocacy: Key figures. a) Rose Kushner. American journalist patient and pioneering advocate for breast cancer patients (as published in Lerner, B.H. (2002). Breast cancer activism: past lessons, future directions. Nat Rev. Cancer 2, 225–230); b) Betty Ford. First Lady of the United States from 1974 to 1977. Breast cancer patient and advocate (adapted from https://en.wikipedia.org/wiki/Betty_Ford); c) The Susan G. Komen for the Cure logo. Founded in 1982, the “Susan G. Komen for the Cure” is the largest breast cancer foundation in the United States (source: http://ww5.komen.org/); d) The International symbol of breast cancer awareness. The pink ribbon was inspired by the Susan G. Komen for the Cure in 1991 (source: http://www.cancer.org/involved/participate/makingstridesagainstbreastcancer/make-a-pink-ribbon-lapel-pin); e) Angelina Jolie. Hollywood actor. Promoted prophylactic mastectomy (source: http://time.com/3450368/the-angelina-effect/).