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Professor Tony Howell

Tony Howell is interested, with Gareth Evans in the prediction of breast cancer risk and the pharmacological prevention of breast cancer. With Michelle Harvie he is interested in lifestyle preventive measures. With MBC scientists, he is interested in the underlying biology of breast cancer risk and prevention.and the development of new preventive agents.

Professor of Medical Oncology

Former Director of the Manchester Breast Centre and Breast Cancer Now Research Unit

The University of Manchester
Wilmslow Road
M20 4BX

Tel: + 44 (0)161 446 8037
Fax: + 44 (0) 161 446 8000

Anthony Howell is Professor of Medical Oncology and, leads the Genesis Prevention Centre Research Programme at the University Hospital of South Manchester NHS Foundation Trust. He is the former Director of the Breast Cancer Now Research Unit, and the Manchester Breast Centre. He trained at Charing Cross Hospital, London and, after a period with the Medical Research Council, moved to Birmingham and then took a post to lead Breast Medical Oncology at The Christie NHS Foundation Trust in Manchester. Formerly he was Chairman of the UK Breast Trials Organisation (UKCCCR), the British Breast Group and the ATAC trial and, up until the end of 2007, was the Research & Development Director of The Christie NHS Foundation Trust and Research Director of the Greater Manchester & Cheshire Cancer Research Network. His interests are the endocrine therapy and biology of the breast and breast cancer with a particular interest in prevention. He has published over 650 papers mainly in these areas.

Breast cancer risk feedback to women in the UK NHS breast screening population

Evans, D. G. R., Donnelly, L. S., Harkness, E. F., Astley, S. M., Stavrinos, P., Dawe, S., Watterson, D., Fox, L., Sergeant, J. C., Ingham, S., Harvie, M. N., Wilson, M., Beetles, U., Buchan, I., Brentnall, A. R., French, D. P., Cuzick, J. & Howell, A.

British Journal of Cancer. 114, 9, p. 1045-52 8 p. 2016

Intensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality

Evans, G., Harkness, E., Howell, A., Wilson, M., Hurley, E., Holmen, M. M., Tharmaratnam, K. U., Hagen, A. I., Lim, Y., Maxwell, A. & Moller, P.

Hereditary cancer in clinical practice. 14, 8. 2016

No strong evidence for increased risk of breast cancer 8-26 years after multiple mammograms in their 30s in females at moderate and high familial risk.

Evans, D. G., Kotre, C. J., Harkness, E., Wilson, M., Maxwell, A. J. & Howell, A.

British Journal of Radiology. 89, 1059. 2016.

Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens

Evans, G., Lalloo, F., Howell, S., Verhoef, S., Woodward, E. R. & Howell, A.

Breast Cancer Research and Treatment. 2016

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Forbes, J. F., MD, . U., Sestak, I., PhD, . U., Howell, A., Bonanni, B., Bundred, N., Levy, C., Minckwitz, G. V., Eiermann, W., Neven, P., Stierer, M., Holcombe, C., Coleman, R. E., Jones, L., Ellis, I., Cuzick, J. & Investigators.

The Lancet. p. 866-873 7 p. 2016

Anastrozole-Induced Carpal Tunnel Syndrome: Results From the International Breast Cancer Intervention Study II Prevention Trial.

Spagnolo, F., Sestak, I., Howell, A., Forbes, J. F. & Cuzick, J.

Journal of Clinical Oncology. 34, 2, p. 139-143 4 p. 2016

Intermittent energy restriction induces changes in breast gene expression and systemic metabolism

Harvie, M., Sims, A., Pegington, M., Spence, K., Mitchell, A., Vaughan, A. A., Allwood, W., Xu, Y., Rattray, N., Goodacre, R., Evans, G., Mitchell, E., McMullen, D., Clarke, R. & Howell, A. 2016

Breast Cancer Research. 18, 1, 57. 2016

The impact of a panel of 18 single nucleotide polymorphisms on breast cancer risk in women attending a UK familial-screening clinic: A case-control study

Evans, D., Brentnall, A. R., Byers, H., Harkness, E., Stavrinos, P., Howell, A., Newman, W. & Cuzick, J.

Journal of Medical Genetics. 2016

Extended long-term follow-up of the IBIS-I breast cancer prevention trial

Jack Cuzick, Ivana Sestak, Simon Cawthorn, Hisham Hamed, Kaija Holli, Anthony Howell, John F. Forbes on behalf of the IBIS-I Investigators*

Lancet Oncology 2015 Jan;16(1):67-7

Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo- controlled trial.

Sestak I, Singh S, Cuzick J, Blake GM, Patel R, Gossiel F, Coleman R, Dowsett M, Forbes JF, Howell A, Eastell R.

Lancet Oncol. 2014 Dec;15(13):1460-8.

Beliefs about weight and breast cancer : experience of a 12 month weight loss programme for breast cancer risk resuction in women at high risk

Claire E Wright, Michelle Harvie, Anthony Howell, D. Gareth Evans, Nick Hulbert-Williams, Louise S Donnelly.

Hered Cancer Clin Pract. 2015 Jan 9;13(1):1

Targeting tumor-initiating cells: Eliminating anabolic cancer stem cells with inhibitors of protein synthesis or by mimicking caloric restriction

Rebecca Lamb, Hannah Harrison, Duncan L. Smith , Paul A. Townsend , Thomas Jackson, Bela Ozsvari, Ubaldo E. Martinez-Outschoorn , Richard G. Pestell ,Anthony Howell , Michael P. Lisanti,* and Federica Sotgi

Oncotarget Jan 2015 in press

Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease.

Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP.

Oncotarget. 2015 Jan 22 in press

Can diet and lifestyle prevent breast cancer – What is the evidence?

Michelle Harvie, Anthony Howell and Gareth Evans

ASCO Educational Book 2015 in press

Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography.

Pål Møller, Kukatharmini Tharmaratnam, Tony Howell, Paula Stavrinos, Sarah Sampson, Andrew Wallace, Anthony J Maxwell, Anne Irene Hagen, D Gareth Evans

Breast Cancer Research and Treatment June 3rd

Intensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality

Evans DG, Harkness E, Howell A, Wilson M, Hurley E, Lim Y, Maxwell A, Moller P

In press

Estrogen Receptor Expression in 21-Gene Recurrence Score Predicts Increased Late Recurrence for Estrogen-Positive/HER2-Negative Breast Cancer.

Dowsett M, Sestak I, Buus R, Lopez-Knowles E, Mallon E, Howell A, Forbes JF, Buzdar A, Cuzick J.

Clin Cancer Res. 2015 Jun 15;21(12):2763-70.

Local mammographic density as a predictor of breast cancer

Mayu Otsuka, Elaine F Harkness , Xin Chen, Emmanouil Moschidi, Megan Bydder, Soujanya Gadde, Yit Y Lim, Anthony J Maxwell, D Gareth Evans, Anthony Howell, Paula Stavrinos, Mary Wilson, Susan M Astley.

SPEI in press

Can diet and lifestyle prevent breast cancer: what is the evidence?

Harvie M, Howell A, Evans DG.

Am Soc Clin Oncol Educ Book. 2015;35:e66-73.

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.

Long-term results of tamoxifen prophylaxis for breast cancer - 96 month follow-up of the IBIS-I study. Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A. Journal of National Cancer Institute. 99 (4): 272-282, 2007.

Association of gain and loss of weight before and after menopause with risk of breast cancer in the Iowa Womens Health Study (IWHS). Harvie M, Howell A, Vierkant R, Kumar N, Cerhan JR, Kelemen LE, Folsom AR, Sellers TA. Cancer Epidemiol Biomarkers & Prev. 14 (3): 656-61, 2005

Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years adjuvant treatment for breast cancer. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS, ATAC Trialists Group. Lancet 365:60-62, 2005.

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomised trial. Howell A, Roberston JF, Abram P, Lichinister MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. J Clin Oncol. 22 (9):1605-13, 2004

Evaluation of breast cancer risk assessment packages in the family history evaluation and screening programme. Amir E, Evans DG, Shenton A, Lalloo F, Moran A, Boggis C, Wilson M, Howell A. J Med Genet. 40(11): 807-814, 2003

Dissociation between steroid receptor expression and cell proliferation suggests cellular hierarchies in the human breast. Clarke RB, Howell A, Potten C, Anderson E. Cancer Research 57: 4987-4992, 1997

Response to a specific antioestrogen (ICI 182780) in tamoxifen-resistant breast cancer. Howell A, DeFriend D, Robertson J, Blamey R, Walton P. Lancet 345: 29-30, 1995.

Sclerosis of lytic bone metastases in response to aminohydroxypropylidene-1, bisphosphonate (APD) in patients with carcinoma of the breast. A R Morton, J A Cantrill, G V Pillai, A McMahon, D C Anderson & A Howell. British Medical Journal 297; 772-773, 1988.

A controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate and fluouracil for breast cancer. A Howell, H Bush, W D George, J M T Howat, D Crowther, R A Sellwood, R D Rubens, J L Hayward R D Bulbrook, I S Fentiman & M Chaudary. Lancet ii: 307-311; 1984.

Bone marrow cells resistant to chloramphenicol in chloramphenicol induced aplastic anaemia. A Howell, T M Andrews & R W E Watts. Lancet, i: 65-69; 1975.