Tony Howell’s contribution to medical science is in laboratory and clinical studies on the breast and in clinical science administration.

He is responsible for introducing several new treatments which have improved patient outcome. The Manchester group were the first to introduce LHRH analogues (goserelin) into the clinic. Tony Howell pioneered so-called ‘window studies’ where the effect of new treatments on the tumour were tested between initial biopsy and definitive excision two weeks later. He published studies showing that tamoxifen may become an agonist which led to the introduction of the pure anti-oestrogen, fulvestrant. The Manchester group led the window study and subsequent international phase II-III studies of the agent which is now in the clinic. Tony Howell helped introduce the aromatase inhibitor, anastrozole, first in advanced disease and later in the adjuvant ATAC trial (as Chairman) which has changed patient management worldwide. His group performed the first randomised trial of adjuvant anthracyclines and confirmatory clinical trials of melphalan and CMF. He introduced granulocyte colony stimulating factor (G-CSF) to intensify chemotherapy and went on to show that G-CSF induced bone marrow progenitors to enter the blood stream and that reinfusion of these could repopulate damaged marrow. He also introduced the use of bisphosphonates to treat advanced breast cancer and described the unusual metastatic pattern of lobular breast cancer.

Tony Howell initiated clinics solely for women at risk of breast cancer. The Manchester clinic model influenced the recent NICE guidelines for risk management. Several influential papers have arisen from the clinic including risk estimation, management of BRCA1/2 mutation carriers and mammography and prophylactic surgery. He is Co-PI on the IBIS prevention trials. IBIS-I recently reported the 10 year positive preventative effect of tamoxifen and the IBIS-II trial is currently recruiting internationally. He was the first to report in epidemiological studies that weight loss reduced breast cancer risk and is now confirming these data in prospective studies.

In extensive studies on the normal human breast his group demonstrated the proliferative effect of OCPs and HRT in normal human breast tissue xenografts. They also demonstrated that oestrogen receptor (ER) positive cells within the normal breast have progenitor characteristics, rarely divide and influence adjacent ER-ve cells by a paracrine mechanism probably involving amphiregulin. These findings are controversial but have been repeated by other groups.

Gareth Evans

Andrew Renehan

Clinical trials

•   - BSc, MB, BS, MSc(London), FRCP