Research

 

Dr. Osborne’s research has spanned 40 years both in the laboratory and clinically in the United Kingdom and the United States of America.

 

During his years in the United Kingdom at Charing Cross Hospital and Medical School, and the Royal Marsden Hospital / Institute for Cancer Research in the 1970s, he studied the spread of breast cancer to the lymph nodes describing, in 1978, the uptake of a radioactive tracer by the primary regional lymph node(s), now called the sentinel lymph node(s). He correlated the lymph nodes with their histopathology to determine whether the breast cancer had spread to the lymph nodes in patients with operable breast cancer. His thesis and publications led to a Master of Surgery degree (PhD equivalent) from the University of London.

 

During his tenure as Lecturer in Surgery at the Royal Marsden and Institute for Cancer Research Dr. Osborne also studied breast conserving surgery and radiation therapy for breast cancer, which was published in the premier journal Cancer Dr. Osborne became convinced that this type of treatment would come to replace mastectomy for the majority of women with early stage breast cancer.

 

In the Unites States in the 1980s at Memorial Sloan Kettering Cancer Center Dr. Osborne offered patients with early stage breast cancer breast conserving surgery with radiation therapy. He believed that better surgical technique and modern radiation therapy would yield significantly better results than those obtained between the 1950s to the 1970s.

 

As Head of the Breast Cancer Research Laboratory, Dr. Osborne conducted both laboratory and clinical studies relating to the detection of the spread of breast cancer in the body (bone marrow).

 

At Memorial Sloan Kettering Cancer Center Dr. Osborne initiated a Special Surveillance Program for women at increased risk of breast cancer. His interest in the causes of breast cancer led to his joining the Biochemical Endocrinology Laboratory at the Rockefeller University where he studied the relationship between hormones and breast cancer initiation and promotion in order to develop novel strategies for prevention.

 

Subsequently as Chief of the Breast Service at the New York Hospital and Professor of Surgery at Cornell University Medical College in the 1990s Dr. Osborne continued his clinical research into bone marrow micrometastases in women with early stage breast cancer.

 

At the Strang Cancer Research Laboratory at Rockefeller University his research continued into the hormonal initiation / promotion of breast cancer and the development of novel strategies for prevention.

 

Since 2000 Dr. Osborne has devoted his time to Strang developing guidelines for early detection through cancer screening and best practices for prevention.

 

Dr. Osborne has been fortunate to work over the years with remarkable scientists and physicians, in collaborative teams, without whom this work could not have been accomplished and who are acknowledged at the end.

 

 

The Spread of Breast Cancer to the Lymph Nodes

 

Dr. Osborne conducted laboratory experimental studies at Charing Cross Hospital / Medical School to optimize the uptake of a ratio-active tracer (99m Tc) encapsulated in liposomes. This work was translated to women with breast cancer, both at Charing Cross Hospital / Medical School and the Royal Marsden Hospital / Institute for Cancer Research. This resulted in mapping the primary regional lymph node and correlating them with the spread of breast cancer. The development of hand held probes to detect radioactivity in lymph nodes lead to the current technique of identifying the sentinel node(s) during surgery.

 

References:

 

Ryman BE, Jewkes RF, Jeyasingh K, Osborne MP, Patel HM, Richardson VJ, Tyrell DA.Potential applications of liposomes to therapy

Annals of the New York Academy of Sciences 1978;308:281-307

 

Osborne MP, Jewkes R, Jeyasingh K, Vincenti AC, Burn JI. Internal mammary lymph node scanning in the staging of breast cancer. Clinical Oncology 1978;4:393

 

Osborne MP, Jeyasingh K, Richardson VJ, Vincenti AC, Jewkes RF, Burn JI. The detection of lymph node metastases using radio-labeled colloids.

British Journal of Surgery 1978;65:354

 

Richardson VJ, Osborne MP, Jeyasingh K, Ryman BE, Burn JI. Differential localization of 99mTc-technetium labeled liposomes in normal and tumor bearing lymph nodes of the rat. British Journal of Cancer 1978;38:177

 

Jeyasingh K, Jewkes RF, Richardson VJ, Osborne MP, Ryman BE. In-vivo distribution of 99mTc liposomes. European Journal of Nuclear Medicine 1979;4:134

 

Osborne MP, Richardson VJ, Jeyasingh K, Ryman BE.  Radionuclide labeled liposomes - a new lymph node imaging agent.

International Journal of Nuclear Medicine and Biology 1979;6:75-83

 

Osborne MP, Jeyasingh K, Jewkes RF, Burns JI. The preoperative detection of internal mammary lymph node metastases in breast cancer. British Journal of Surgery 1979;66:813-818

 

Osborne MP.  Lymph node scanning for breast cancer.

Transactions of the Medical Society of London 1979;95:43-5

 

Osborne MP, Richardson VJ, Payne JH, McCready VR, Ryman BE. Technetium-99m labeled liposome axillary lymphoscintigraphy in breast cancer.

Clinical Oncology 1980;6:289

 

Osborne MP. The detection of lymphatic metastases in breast cancer.

Master of Surgery Thesis, University of London, 1980

 

Osborne MP, Ryman BE, Payne JH, McCready VR. The use of 99mTc-labelled neutral liposomes in lymphoscintigraphy: a comparison of scintigram interpretations with node histology in a series of breast cancer patients.

In: Progress in Radiopharmacology. Ed: PM Cox.  Elsevier / North Holland Biomedical Press 1981;2:317-325

 

Osborne MP. The preoperative detection of internal mammary lymph node metastases in breast cancer. Current Surgery 1981;38:31

 

Jeyasingh K, Osborne MP, Jewkes RF. Detection of lymph node metastasis by a sequential scanning technique using two 99mTc-labeled colloids. In: Nuklear Medezin.  Functional Analysis.  Ed. FK Schattauer, 19th International Meeting of SNME, Bern, Switzerland.  Verlag, New York, 1981

 

Osborne MP, Richardson VJ, Jeyasingh K, Ryman BE. Potential applications of radionuclide-labeled liposomes in the detection of the lymphatic spread of cancer.

International Journal of Nuclear Medicine, Biology and Physics 1982;9:47-51

 

Osborne MP, Payne JH, Richardson VJ, McCready VR, Ryman BE. The preoperative detection of axillary lymph node metastases in breast cancer by isotope imaging. British Journal of Surgery 1983;70:141-144

 

 

Breast Conserving Surgery and Radiation Therapy for Early Stage Breast Cancer as an Alternative to Mastectomy

 

In 1983, while at Memorial Sloan Kettering Cancer Center, Dr. Osborne presented the largest and longest follow up series of patients with breast cancer treated at the Royal Marsden Hospital, between the 1950s to the 1970s, by breast conserving surgery and radiation therapy to the 36th Annual Meeting of the Society of Surgical Oncology in a paper entitled Early breast cancer: 20-year follow-up of breast conservation. These data were published in the journal Cancer in 1984.

 

In his book The Breast Cancer Wars Baron Lerner MD, a Professor at the Mailman School of Public Health at Columbia University, described the obstacles surrounding Dr. Osborne’s introduction of breast conserving surgery as an alternative to Memorial Sloan Kettering Cancer Center’s policy of mastectomy for patients with early stage breast cancer.

 

Reference:

 

The Breast Cancer Wars.  Hope, Fear, and the Pursuit of a Cure in Twentieth-Century America Baron L. Oxford University Press 2001; pp. 254-255

 

Breast conserving surgery is now the standard of care for the majority of women with breast cancer. Following the slow acceptance of breast conserving surgery Dr. Osborne continued to be active in research to refine the technique and the surgery required in the event of recurrence. Today about 5% of patients experience a recurrence and for a highly selected group a second chance for conservation may be considered; further research is ongoing to determine whether this is a safe option.

 

 

References:

 

Osborne MP, Ormiston N, Harmer CL, McKinna JA, Baker J, Greening WP. Early breast cancer: 20-year follow-up of breast conservation. Society of Surgical Oncology 36th Annual Meeting Denver, CO. 1983

 

Osborne MP, Ormiston N, Harmer CL, McKinna JA, Baker J, Greening WP. Breast conservation in the treatment of early breast cancer: A 20-year follow-up. Cancer 1984;53:349-355

 

Osborne MP. Limited resection and radical radiation therapy in the treatment of early stage breast cancer. Problems in General Surgery 1985;2:159-166

 

McCormick B, Kinne D, Petrek J, Osborne MP, Cox L, Shank B, Hellman S, Yahalom J, Rosen PP. Limited resection for breast cancer: A study of inked specimen margins before radiotherapy. International Journal of Radiation Oncology, Biology, Physics 1987;13:1667-1671

 

Wesson MF, Osborne MP, Petrek J, Kinne D, McCormick B. Iridium-192 implants for primary breast cancer: Experience with concomitant limited resection or re-excision. Endocurietherapy/Hyperthermia Oncology 1988;4:149-153

 

McCormick B, Wesson MF, Cox L, Osborne MP, Petrek JA, Kinne DW. Iridium-192 implants for primary breast cancer: Experience with placement at the time of wide local excision. International Journal of Radiation Oncology, Biology and Physics 1988;15:745-748

 

Dershaw DD, McCormick B, Cox L, Osborne MP. Differentiation of benign and malignant local tumor recurrence after lumpectomy. American Journal of Roentgenology 1990;155:35-38

 

Osborne MP, Borgen PI, Wong GY, Rosen PP, McCormick B. Salvage mastectomy for local-regional relapse after breast conserving surgery and radiation therapy. Surgery, Gynecology and Obstetrics 1992;174:189-194

 

Dershaw DD, McCormick B, Osborne MP. Detection of local recurrence after conservation therapy for breast carcinoma. Cancer 1992;70:493-496

 

Osborne MP, Simmons RM. Salvage surgery for recurrence after breast conservation. World Journal of Surgery 1994;18:93-97

 

Giess CS, Keating DM, Osborne MP, Rosenblatt R. Local tumor recurrence following breast-conservation therapy: Correlation of histopathologic findings with detection method and mammographic findings. Radiology 1999;212:829 -835.

 

Simmons RM, Brennan MB, Christos P, Sckolnick M, Osborne MP. Recurrence rates in patients with central or retroareolar breast cancers treated with mastectomy or lumpectomy. American Journal of Surgery 2001; 182:325-329

 

Huston TL, Pigalarga R, Osborne MP, Tousimis E. The influence of additional surgical margins on the total specimen volume excised and the reoperative rate after breast-conserving surgery. American Journal of Surgery 2006; 192:509-12

 

Jacobson AF, Asad J, Boolbol SK, Osborne MP, Boachie-Adjei K, Feldman SM. Do additional shaved margins at the time of lumpectomy eliminate the need for re-excision? American Journal of Surgery 2008;196:556-8

 

Chadha M, Trombetta M, Boolbol S, Osborne MP. Managing a small recurrence in the previously irradiated breast. Is there a second chance for breast conservation? Oncology 2009;23:933-40

 

Early-stage breast cancer treated with 3-week accelerated whole-breast radiation therapy and concomitant boost. Chadha M, Woode R, Sillanpaa J, Lucido D, Boolbol SK, Kirstein L, Osborne MP, Feldman S, Harrison LB. International Journal of Radiation Oncology Biology and Physics 2013;86:40-4

 

 

Bone Marrow Micrometastases in Early Stage Breast Cancer

 

During his time as head of the Breast Cancer Research Laboratory at Memorial Sloan Kettering Cancer Center, Dr. Osborne studied the spread of breast cancer outside of the breast and lymph nodes to the bone marrow. Before surgery began, after the patient was anesthetized, samples of the bone marrow were taken and tested for cancer cells using, for the first time, monoclonal antibodies against components in cancer cells which are not found on bone marrow cells.

 

References:

 

Cote R, Rosen PP, Osborne MP, Sedira M, Hakes T, Kinne D, Old L Monoclonal antibodies (Mab) detect occult bone marrow metastases in operable breast cancer. Laboratory Investigation 1987;56:16

 

Osborne MP, Cote RJ, Hakes TB, Kinne DW, Old LJ, Rosen PP. Fluorescent monoclonal antibody detection of occult micrometastases in the bone marrow of patients with breast cancer. Cancer Investigation 1988;6:565

 

Cote RJ, Rosen PP, Hakes TB, Sedira M, Bazinet M, Kinne DW, Old LJ, Osborne MP. Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease. American Journal of Surgical Pathology 1988;12:333-340

 

Osborne MP, Asina S, Wong G, Old L, Cote RJ. The sensitivity of immunofluorescent monoclonal antibody detection of breast cancer micrometastases in bone marrow. European Journal of Cancer 1989;15:186

 

Osborne MP, Asina S, Wong GY, Cote RJ, Rosen PP. Sensitivity of immunocytochemical detection of breast cancer in bone marrow using monoclonal antibodies. Breast Cancer Research and Treatment 1989;14:162

 

Osborne MP, Asina S, Wong GY, Rosen PP, Fracchia AA, Kinne DW, Cote RJ. Immunofluorescent monoclonal antibody detection of breast cancer micrometastases. Breast Cancer Research and Treatment 1989;14:161

 

Osborne MP, Cote RJ, Asina S, Wong GY, Potter C, Killackey D, Rosen PP.

Immunofluorescent monoclonal antibody detection of bone marrow micrometastases in patients with unilateral stages I-III invasive breast cancer.

Breast Cancer Research and Treatment 1990;16:194

 

Cote RJ, Rosen PP, Lesser ML, Osborne MP. Detection of occult bone marrow micrometastases in patients with operable breast cancer predicts early recurrence. Modern Pathology 1990;3:23

 

Osborne MP, Asina S, Wong GY, Old LJ, Cote RJ, Rosen PP.  Sensitivity of immunocytochemical detection of breast cancer cells in human bone marrow.

Cancer Research 1991;51:2706-2709

 

Osborne MP, Wong GY, Cote RJ, Liu J, Potter C, Killackey D, Old LJ, Rosen PP.  Breast cancer micrometastases in bone marrow: detection by fluorescein-labeled monoclonal antibodies predicts early relapse. Proceedings of the American Society of Clinical Oncology 1991;10:45

 

Wong GY, Osborne MP. Breast cancer bone marrow micrometastases: a sensitive statistical analysis of the effect of systemic tumor cell burden. Breast Cancer Research and Treatment 1991;19:171

 

Osborne MP, Cote RJ, Wong GY, Potter CE, Gonzalez A, Rosen PP. Immunofluorescent monoclonal antibody (MAB) detection of breast cancer bone marrow micrometastases (BMM) in patients with unilateral invasive breast cancer:  distribution by TNM stage.

Breast Cancer Research and Treatment 1992;23:136

 

Garin-Chesa P, Gonzalez A, Old LJ, Osborne MP, Rosen PP. Detection of occult bone marrow micrometastases (BMM) in patients with epithelial cancer: technical aspects.

Modern Pathology 1992;5:119

 

Osborne MP, Wong GY, Gonzalez A, Potter C, Vlamis V, Cote RJ. Bone marrow micrometastases (BMM) in breast cancer: The effect of systemic tumor cell (TC) burden on early relapse. Proceedings of the American Society of Clinical Oncology 1993;12:102

 

Singhal H, Cote RJ, Potter C, Osborne MP. Bone marrow micrometastases (BMM) in breast cancer: relationship to local-regional disease status.

Proceedings of American Society of Clinical Oncology 1994;13:215

 

Osborne MP, Rosen PP. Detection and management of bone marrow micrometastases in breast cancer. Oncology 1994;8:25-31

 

Singhal H, Potter C, Osborne MP. No effect of timing of biopsy in the menstrual cycle on incidence of bone marrow micrometastasis in patients with breast cancer. Annals of Surgical Oncology 1997;4:503-505

 

Osborne MP. Prognostic and therapeutic implications of bone marrow micrometastases. Cancer Investigation 1997;15:52

 

Wong GYC, Osborne MP. Bone marrow micrometastatic tumor cell burden independently predicts breast cancer relapse. Proceedings of the 21st Annual San Antonio Breast Cancer Symposium. Breast Cancer Research and Treatment 1998;50:280

 

Reichman BS, Osborne MP. Detection of occult micrometastatic disease. In: The Breast. Comprehensive management of benign and malignant diseases.

Eds: KI Bland, EM Copeland. WB Saunders, Philadelphia 1998, pp 1299-1303

 

Simmons R, Hoda S, Osborne MP. Bone marrow micrometastases in breast cancer patients. American Journal of Surgery 2000;180:309-312

 

Singhal H, Osborne MP. Bone marrow micrometastases detection and significance In:  Cancer metastasis, molecular and cellular mechanisms and clinical intervention.  Eds. WG Jiang, RE Mansel.  Kluwer Academic Publishers, Dordrecht, The Netherlands, 2000,  pp 215-224

 

Osborne MP, Wong G Breast cancer bone marrow micrometastases: a long term prognostic study. Proceedings of the American Society of Clinical Oncology 2002;21:58a

 

Simmons R, Osborne MP. Bone marrow aspiration as an adjunct to staging by sentinel lymph node biopsy in breast cancer patients. Seminars in Breast Disease 2002; 5:47-52

 

Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga J-Y, Marth C, Oruzio D, Wiedswang G, Solomayer E-F, Kundt G, Strobl B, Fehm T, Wong GYC, Bliss J, Vincent-Salomon A, Pantel K. A pooled analysis of bone marrow micrometastasis in breast cancer. New England Journal of Medicine 2005; 353:793-802

 

Osborne MP Micrometastases in bone marrow. European Journal of Cancer 2004;2S:67-68

 

Yu Q, Wong GYC, Osborne M.P, Hsu Y, Ai X. The Lehmann model with time-dependent covariates. Communications in Statistics - Theory and Methods. 2015 (In press)

 

 

Women at Risk for Breast Cancer

 

In the early 1980s Dr. Osborne started a Special Breast Surveillance Program at Memorial Sloan Kettering Cancer Center specializing in the care of women at increased risk for breast cancer. The women in this program had never had breast cancer and the majority had a strong family history of breast cancer; some women had breast biopsies that showed a tissue change indicating an increased risk in the future. In 2004 the BRCA1 gene was discovered and Dr. Osborne and his co-investigators contributed DNA from the largest group of women at risk due to a family history consistent with the Breast Ovarian Cancer Syndrome and were co-authors of the first BRCA1 clinical paper published. Dr. Osborne joined the Hereditary Breast Cancer Clinical Study Group in the late 1990s. He has maintained a clinical and research interest in women at enhanced risk for breast cancer over the past 30 years.

 

References:

 

 

Osborne MP, Crowe JP. The identification of enhanced risk patients and their management in a special surveillance breast clinic. In: Breast Cancer: Diagnosis and Treatment.  Eds: IM Ariel, JB Cleary.  McGraw Hill, New York, 1987, pp75-86

 

Williams WR, Osborne MP. Familial aspects of breast cancer: An overview

In: Breast Diseases.  Eds: J Harris, S Hellman, C Henderson, D Kinne.  Lippincott, Philadelphia 1987, pp 109-120

 

Osborne MP, Borgen PI. Atypical ductal and lobular hyperplasia and breast cancer risk.

Surgical Oncology Clinics of North America 1993;2: 1-11

 

Osborne MP, Hoda S. Current management of lobular carcinoma in situ of the breast.

Oncology 1994;8:45-49

 

Shattuck-Eidens D, McClure M, Simard J, Labrie F, Narod S, Couch F, Hoskins K, Weber B, Castilla L, Erdos M, Brody L, Friedman L, Ostermeyer E, Szabo C, King MC, Jharwar S, Offit K, Norton L, Gilewski T, Lubin M, Osborne MP, Black D, Boyd M, Steel M, Ingles S, Haile R, Lindblom A, Olsson H, Borg A, Bishop DT, Solomon E, Radice P, Spatti G, Gayther S, Ponder B, Warren W, Stratton M, Liu Q, Fujimura F, Lewis C, Skolnick M, Goldgar E. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene.

Journal of the American Medical Association 1995;273:535-541

 

Valdimarsdottir HB, Bovberg DH, Kash KM, Holland JC, Osborne MP, Miller DG.

 Psychological distress in women with a familial risk of breast cancer.

Psycho-oncology 1995;4:133-141

 

Kash KM, Holland JC, Miller DG, Osborne MP. Psychological distress and adherence to screening behaviors in women at genetic risk for breast cancer.

Psychosomatic Medicine 1994;56:148-149

 

Zakowski SG, Valdimardottir HB, Bovbjerg DH, Borgen P, Holland J, Kash K, Miller DG, Mitnick J, Osborne MP, Van Zee K. Predictors of intrusive thoughts and avoidance in women with family histories of breast cancer. Annals of Behavioral Medicine 1997;19:362-369

 

Robson M, Dabney MK, Rosenthal G, Ludwig S, Seltzer MH, Gilewski T, Haas B,

Osborne MP, Norton L, Gilbert F, Offit K. Prevalence of recurring BRCA mutations  among Ashkenazi Jewish women with breast cancer. Genetic Testing 1997;1:47-51

 

Gilbert F, Dabney MK, Diemer K, Ludwig S, Rosenthal G, Osborne MP.  BRCA1/BRCA2 mutations and breast cancer in Ashkenazi Jewish women.

Annals of the New York Academy of Sciences 1997;833:198-203.

 

Narod SA, Dubé MP, Klijn J, Lubinski J, Lynch HT, Ghadirian P, Provencher D, Heimdal K, Moller P, Robson M, Offit K, Isaacs C, Weber B, Friedman E, Gershoni-Baruch R, Rennert G, Pasini B, Wagner T, Daly M, Garber JE, Neuhausen SL, Ainsworth P, Olsson H, Eavns G, Osborne MP, Couch F, Foulkes WD, Warner E, Kim-Sing C, Olopade O, Tung N, Saal HM, Weitzel J, Merajver S, Gauthier-Villars M, Jernstrom H, Sun P, Brunet JS. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

Journal of the National Cancer Institute 2002; 94:1773-1779

 

Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, Daly M, Kim-Sing C, Olsson H, Ainsworth P, Eisen A, Saal H, Friedman E, Olopade O, Osborne MP, Weitzel J, Lynch H, Ghadirian P, Lubinski J, Sun P, Narod SA. Hereditary Breast Cancer Clinical Study Group. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update.

International Journal of Cancer 2006; 118:2281-2284

 

Friedman E, Kotsopoulos J, Lubinski J, Lynch HT, Ghadirian P, Neuhausen SL, Isaacs C, Weber B, Foulkes WD, Moller P, Rosen B, Kim-Sing C, Gershoni-Baruch R, Ainsworth P, Daly M, Tung N, Eisen A, Olopade OI, Karlan B, Saal HM, Garber JE, Rennert G, Gilchrist D, Eng C, Offit K, Osborne M, Sun P, Narod SA. Hereditary Breast Cancer Clinical Group. Spontaneous and therapeutic abortions and the risk of breast cancer among BRCA mutation carriers.

Breast Cancer Research 2006;8: Epub 2006 Mar 21

 

Kotspoulos J, Lubinski J, Lynch HT,Klijn J, Ghadirian P, Neuhausen SL, Kim-Sing C, Foulkes WD, Moller P, Isaacs C, Domcheck S, Randall S, Offit K, Tung N, Ainsworth P, Gershoni-Baruch R, Eisen A, Daly M, Karlan B, Saal HM, Couch F, Pasini B, Wagner T, Friedman E, Rennert G, Eng C, Weitzel J, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group, Garber J, Osborne M, Fishman D, McLennan J, McKinnon W, Merajver S, Olsson H, Provencher D, Pasche B, Evans G, Meschino WS, Lemire E, Chudley A Rayson D, Bellati C. Age at first birth and the risk of breast cancer in BRCA 1 and BRCA 2 mutation carriers.

Breast Cancer Research and Treatment 2007;105:221-228

 

Eisen A, Lubinski J, Gronwald J, Moller P, Lynch HT, Klijn J, Kim-Sing C, Neuhausen SL, Gilbert L, Ghadirian P, Manoukian S, Rennert G, Friedman E, Isaacs C, Rosen E, Rosen B, Daly M, Sun P, Narod SA. Hereditary Breast Cancer Clinical Study Group. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers.

Journal of the National Cancer Institute 2008;100:1361-1367

 

Hormones and Breast Cancer

 

Dr. Osborne’s interest in hormones and breast cancer was fostered by his joining the Biochemical Endocrinology Laboratory at the Rockefeller University soon after joining the staff of Memorial Sloan Kettering Cancer Center in the early 1980s. The research focuses on the cellular and molecular biological changes in the process of cancer development. The Rockefeller University group hypothesized that a specific metabolite of estrogen was a potential initiator and promoter of breast cancer. Dr. Osborne and his colleagues showed that production of this specific metabolite was increase 500 fold in the breast tissue of women with breast cancer compared to women without breast cancer. This work prompted the author of a book entitled Breakthrough: The Race to Find the Breast Cancer Gene by Kevin Davies PhD, Editor of a leading journal in the field - Nature Genetics, to describe Dr. Osborne’s work.

 

Reference:

 

Breakthrough: The Race to Find the Breast Cancer Gene. K Davies, M White Wiley 1995 pp 32-33

 

The role of this specific estrogen metabolite remains controversial but there has been a growing body of evidence supporting this hypothesis. This work led Dr. Osborne’s research group to develop strategies for prevention.

 

References:

 

Osborne MP, Rosen PP, Lesser ML, Schwartz MK, Menendez-Botet CJ, Fishman J, Kinne DW, Beattie EJ Jr.  The relationship between family history, exposure to exogenous hormones and estrogen receptor protein in breast cancer.  Cancer 1983;51:2134-2138

 

Axelrod DM, Menendez-Botet CJ, Kinne DW, Osborne MP. Levels of estrogen and progesterone receptor proteins in patients with breast cancer during various phases of the menstrual cycle. Cancer Investigation 1988;6:7-14

 

Telang NT, Bradlow HL, Kurihara H, Osborne MP. In vitro biotransformation of estradiol by explant cultures of murine mammary tissues.

Breast Cancer Research and Treatment 1989;13:173-181

 

Telang NT, Axelrod DM, Bradlow HL, Osborne MP. Metabolic biotransformation of estradiol in human mammary explant cultures.

Annals of the New York Academy of Sciences 1990;586:70-78

 

Telang NT, Axelrod DM, Wong GY, Bradlow HL, Osborne MP. Biotransformation of estradiol by explant cultures of human breast tissue.  Steroids 1991;56:37-43

 

Telang NT, Kurihara H, Wong GY, Bradlow HL, Osborne MP.

Preneoplastic transformation in mouse mammary tissue: identification and validation of intermediate biomarkers for chemoprevention. Anticancer Research 1991;11:1021-1028

 

Telang NT, Suto A, Wong GY, Osborne MP, Bradlow HL. Induction by estrogen metabolite 16a-hydroxestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. Journal of the National Cancer Institute 1992;84:634-636

 

Suto A, Bradlow HL, Wong GY, Osborne MP, Telang NT. Persistent endocrine responsiveness of ras oncogene-transformed mouse mammary epithelial cells. Steroids 1992;57:262-268

 

Telang NT, Bradlow HL, Osborne MP. Molecular and endocrine biomarkers in non-involved breast: relevance to cancer chemoprevention. Journal of Cellular Biochemistry 1992;16:161-169

 

Suto A, Bradlow HL, Kubota T, Kitajima M, Wong GY, Osborne MP, Telang NT.

Alterations in proliferative and endocrine responsiveness of human mammary carcinoma cells by prototypic tumor suppressing agents. Steroids 1993;58:215-219

 

Garg A, Suto A, Osborne MP, Gupta RC, Telang NT. Expression of biomarkers for transformation in 7,12-dimethylbenz[a]anthracene-treated mammary epithelial cells

International Journal of Oncology 1993;3:185-189

 

Osborne MP, Bradlow HL, Wong GYC, Telang NT. Upregulation of estradiol C16α-hydroxylation in human breast tissue:  A potential biomarker of breast cancer risk.

Journal of the National Cancer Institute 1993;85:1917-1920

 

Suto A, Bradlow HL, Wong GYC, Osborne MP, Telang NT. Experimental down-regulation of intermediate biomarkers of carcinogenesis in mouse mammary epithelial cells.

Breast Cancer Research and Treatment 1993;27:193-202

 

Fishman J, Osborne MP, Telang NT. The role of estrogen in mammary carcinogenesis.

Annals of the New York Academy of Sciences 1995;768:91-100

 

Sepkovic DW, Bradlow HL, Ho G, Hankinson SE, Gong L, Osborne MP, Fishman J.

Estrogen metabolite ratios and risk assessment of hormone-related cancers.  Assay validation and prediction of cervical cancer risk.

Annals of the New York Academy of Sciences 1995;768:312-316

 

Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-Hydroxyestrone: the ‘good’ estrogen. Journal of Endocrinology 1996;150:S259-S265

 

Fishman JH, Gonzalez A, Osborne MP. Breast cancer cells cultured in a system of new design presecrete an extracellular matrix and proliferate within it without cell-cell adhesion.

Biochemical and Biophysical Research Communication 1996;220:467-471

 

Bradlow L, Telang NT, Osborne MP. Estrogen metabolites as bioreactive modulators of tumor initiators and promoters. Advances in Experimental Medical Biology 1996;387:285-296

 

Katdare M, Singhal H, Newmark H, Osborne MP, Telang NT. Prevention of mammary preneoplastic transformation by naturally-occurring tumor inhibitors.

Cancer Letters 1997;111:141-147

 

Telang NT, Katdare M, Bradlow HL, Osborne MP. Estradiol metabolism: An endocrine biomarker for modulation of human mammary carcinogenesis.

Environmental Health Perspectives 1997;105:559-564

 

Telang NT, Inoue S, Bradlow HL, Osborne MP. Negative growth regulation of oncogene-transformed mammary epithelial cells by tumor inhibitors.

Advances in Experimental Medicine and Biology 1997;400A:409-418

 

Davis DL, Telang NT, Osborne MP, Bradlow HL. Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer. Environmental Health Perspectives 1997;105:571-576.

 

Telang NT, Arcuri F, Granata OM, Bradlow HL, Osborne MP, Castagnetta L. Alteration of oestradiol metabolism in myconcogene-transfected mouse mammary epithelial cells.

British Journal of Cancer 1998; 77:1549-1554

 

Bradlow HL, Sepkovic DW, Klug T, Osborne MP. Application of an improved ELISA assay to the analysis of urinary estrogen metabolites. Steroids 1998; 63:406-413

 

Taioli E, Bradlow HL, Garbers VV, Sepkovic DW, Osborne MP, Trachman J, Ganguly S, Garte SJ. Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk.

Cancer Detection and Prevention 1999;23:232-237.

 

Suto A, Telang NT, Tanino H, Takeshita T, Ohmiya H, Osborne MP, Kubota T. In vitro and in vivo modulation of growth regulation in the human breast cancer cell line MCF-7 by estradiol metabolites. Journal of the Japanese Breast Cancer Society 1999;6:87-92

 

Telang NT, Katdare M, Bradlow HL, Osborne MP. Cell cycle regulation, apoptosis and estradiol biotransformation: novel endpoint biomarkers for human breast cancer prevention.

Journal of Clinical Ligand Assay 2000;23:130-137

 

 

 

Prevention of Breast Cancer

 

Dr. Osborne has maintained an interest in breast cancer prevention studying the effects of various pharmaceutical, nutriceutical and botanical agents’ ability to inhibit or reverse pre-cancer or cancer development. He was Principal Investigator at Strang as a collaborator in studies by the National Surgical Adjuvant Breast and Bowel Project (NSABP) on the risk reducing effects of tamoxifen and raloxifene which showed the risk of breast cancer can be reduced by half in women at increased risk.

 

References:

 

Recabaren J, Osborne MP, DeCosse JJ. Individuals at High Risk - Preventive Measures. In: Series: New Horizons in Oncology.  Ed: B Stoll.  Vol 3: Risk Factors in Multiple Cancer.  Wiley, London, 1983, pp. 263-275

 

Osborne MP. Prophylactic mastectomy. In: Breast Diseases. Eds: J Harris, S Hellman, C Henderson, D Kinne.  Lippincott, Philadelphia 1987, pp 120-121.

 

Osborne MP. Prophylactic mastectomy. In: Breast Diseases.  Eds: J Harris, S Hellman, C Henderson, D Kinne.  Lippincott, Philadelphia 1987, pp 120-121.

 

Osborne MP, Bayle J-C. Prophylactic mastectomy: Rarely indicated in the non-affected patient. Primary Care and Cancer 1988;8:25-31

 

Osborne MP, Karmali RA, Hershcopf RJ, Bradlow HL, Kourides IA, Williams WR, Rosen PP, Fishman J. Omega-3 fatty acids: modulation of estrogen metabolism and potential for breast cancer prevention. Cancer Investigation 1988;6:629-631

 

Dermatis H, Rowland J, Miransky J, Kerner J, Osborne MP, Holland J.  Consent and compliance in chemoprevention trials. Cancer Investigation 1988;6:633-635

 

Osborne MP, Telang NT, Kaur S, Bradlow HL. Influence of chemo-preventive agents, tamoxifen and hydroxyphenylretinamide (HPR) on estradiol metabolism and mammary preneoplasia in C3H mice. Steroids 1990;55:114-119

 

Osborne MP, Telang NT. Primary prevention of breast cancer. In: The Breast: Comprehen:ive Management of Benign and Malignant Diseases. Eds: KI Bland, EM Copeland. WB Saunders, Philadelphia 1991, pp 246-261

 

Michnovicz JJ, Telang NT, Osborne MP, Bradlow HL. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice.

Carcinogenesis 1991;12:1571-1574

 

Osborne MP, Ruperto JF, Crowe JP, Rosen PP, Telang NT. The effect of tamoxifen on preneoplastic cell proliferation in N-nitroso-N-methylurea-induced mammary carcinogenesis. Cancer Research 1992;52:1477-1480

 

Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP.

Long-term responses of women to indole-3-carbinol or a high fiber diet.

Cancer Epidemiology Biomarkers and Prevention 1994;3:591-595

 

Tiwari RK, Guo L, Bradlow HL, Telang NT, Osborne MP. Selective responsiveness of human breast cancer cells to indole-3-carbinol, a chemopreventive agent.

Journal of the National Cancer Institute 1994;86:126-131

 

Sepkovic DW, Bradlow HL, Michnovicz J, Murtezani S, Levy I, Osborne MP. Catechol estrogen production in rat microsomes after treatment with indole-3-carbinol, ascorbigen, or B-naphthaflavone:  A comparison of stable isotope dilution gas chromatography-mass spectrometry and radiometric methods. Steroids 1994;59:318-322

 

Telang NT, Bradlow HL, Osborne MP. Effect of tamoxifen on mammary preneoplasia:  Relevance to chemopreventive intervention. Cancer Detection and Prevention 1994;18:313-321

 

Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP. Long-term responses of women to indole-3-carbinol or a high fiber diet.

Cancer Epidemiology Biomarkers and Prevention 1994;3:591-595

 

Li G, Osborne MP, Tiwari RK. Anti-proliferative effects of garlic constituents in cultured human breast cancer cells. Oncology 1995;2:787-791

 

Araki R, Inoue S, Osborne MP, Telang NT. Chemoprevention of mammary preneoplasia.  In-vitro effects of a green tea polyphenol.

Annals of the New York Academy of Sciences 1995;768:215-222

 

Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Indole-3-carbinol.  A novel approach to breast cancer prevention. Annals of the New York Academy of Sciences 1996;768:180-200

 

Osborne MP. Hormonal intervention in breast cancer: Past, present and future.

Annals of the New York Academy of Sciences 1996;784:427-432

 

Telang NT, Katdare M, Bradlow HL, Osborne MP, Fishman J. Inhibition of proliferation and modulation of estradiol metabolism: Novel mechanisms for breast cancer prevention by the phytochemical indole-3-carbinol. Proceedings of the Society for Experimental Biology and Medicine 1997; 216:246-252

 

Wong GYC, Bradlow L, Sepkovic D, Mehl S, Mailman J, . Dose-ranging study of indole-3-carbinol for breast cancer prevention.

Journal of Cellular Biochemistry 1997;Supplements 28/29:111-116

 

Katdare M, Osborne MP, Telang NT. Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals.

Oncology Reports 1998:5;311-315

 

Osborne MP. Chemoprevention of breast cancer.

Surgical Clinics of North America 1999;79:1207-1221

 

Osborne MP. Breast cancer prevention by antiestrogens.

Annals of the New York Academy of Sciences 1999;889:146-151

 

Katdare M, Jinno H, Osborne MP, Telang NT. Negative growth regulation of oncogene-transformed human breast epithelial cells by phytochemicals: role of apoptosis.

Annals of the New York Academy of Science 1999;889:247-252

 

Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. Phytochemicals as modulators of cancer risk.  Advances in Nutrition and Cancer 2. Ed:  Zappia et al. Kluwer Academic / Plenum Publishers, New York, 1999

 

Jinno H, Steiner MG, Mehta RG, Osborne MP, Telang NT.  Inhibition of aberrant proliferation and induction of apoptosis in HER-2/neu oncogene transformed human mammary epithelial cells by N-(4-hydroxyphenyl) retinamide. Carcinogenesis 1999;20:229 -236

 

Rosenbaum Smith SM, Osborne MP. Breast cancer chemoprevention.

American Journal of Surgery 2000;180:249-251

 

Jinno H, Steiner MG, Nason-Burchenal K,Osborne MP, Telang NT. Preventive efficacy of receptor class selective retinoids on HER-2/neu oncogene expressing preneoplastic human mammary epithelial cells. International Journal of Oncology 2002;21:127-134

 

Katdare M, Osborne MP, Telang NT. Soy isoflavone genistein modulates cell cycle progression and induces apoptosis in HER-2/neu oncogene expressing human breast epithelial cells. International Journal of Oncology 2002;21:809-815

 

Osborne MP. Prophylactic mastectomy. In Seminars in Breast Disease 2003:34-40

 

Katdare M, Osborne MP, Telang NT. Novel cell culture models for prevention of human breast cancer. International Journal of Oncology 2003; 22:509-515

 

Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, Gronwald J, Lynch H, Moller P, Ghadirian P, Foulkes WD, Klijn J, Friedman E, Kim-Sing C, Ainsworth P, Rosen B, Domchek S, Wagner T, Tung N, Manoukian S, Couch F, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group. International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers International Journal of Cancer 2008;122:2017-22.

 

Ginsburg O, Ghadirian P, Lubinski J, Cybulski C, Lynch H, Neuhausen S, Kim-Sing C, Robson M, Domchek S, Isaacs C, Klijn J, Armel S, Foulkes WD, Tung N, Moller P, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group.

Smoking and the risk of breast cancer in BRCA1 and BRCA2 carriers: an update.

Breast Cancer Research and Treatment 2009;114:127-35

 

Ginsburg OM, Kim-Sing C, Foulkes WD, Ghadirian P, Lynch HT, Sun P, Narod SA: Hereditary Breast Cancer Clinical Study Group. BRCA1and BRCA2 families and the risk of skin cancer.

Familial Cancer. 2010;9:489-93

 

Metcalfe K, Lubinski J, Lynch HT, Ghadirian P, Foulkes WD, Kim-Sing C, Neuhausen S, Tung N, Rosen B, Gronwald J, Ainsworth P, Sweet K, Eisen A, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group.                                                                                                                                                            Family history of cancer and cancer risks in women with BRCA1 or BRCA2 mutations.

Journal of the National Cancer Institute 2010;102:1874-8

 

Dennis J, Ghadirian P, Little J, Lubinski J, Gronwald J, Kim-Sing C, Foulkes W, Moller P, Lynch HT, Neuhausen SL, Domchek S, Armel S, Isaacs C, Tung N, Sweet K, Ainsworth P, Sun P, Krewski D, Narod S; Hereditary Breast Cancer Clinical Study Group. Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. Breast. 2010;19:479-83

 

Pal T, Keefe D, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group. Fertility in women with BRCA mutations: a case-control study.                                                                       Fertility Sterility. 2010;93:1805-1808

 

Cancer Screening and Prevention

 

Dr. Osborne has developed, with cancer specialists, comprehensive guidelines for cancer screening and best practices for prevention which are available at www.strang.org. The guidelines are directed towards Primary Care, Family Practice, Gynecology, Internal Medicine and other Health Care Providers.

The guidelines also provide comprehensive answers to the most frequently asked questions (FAQs) by patients who have been recommended breast, cervical, colon, lung and prostate cancer screening. Dr. Osborne is planning for Strang to partner with major health care systems to provide them with a unified and comprehensive program for their physicians and allied health care professionals.

 

Dr. Osborne is also collaborating in a study of Primary Care Physicians cancer screening recommendations and their patients understanding of the recommendations in order to develop easier and more effective methods for cancer screening recommendations.

 

Collaborators:

 

Dr. Osborne acknowledges and thanks all those with whom he has had collaborations which have largely made this work possible.

 

Some of Dr. Osborne’s collaborators have worked with him for over 30 years such as Nitin Telang PhD, Leon Bradlow PhD, George Wong PhD, and Charles Potter MA.