Detection, Outcomes and Risk

Detection, Predicting Outcomes and Risk Assessment

Developed mammography technology and showed that mammography can detect breast cancer at early, highly curable stages, leading to adoption of standardized screening mammography.

Egan RL. Experience with mammography in a tumor institution. Evaluation of 1,000 studies. Radiology. 1960 Dec;75:894-900.

Egan RL. Fifty-three cases of carcinoma of the breast: occult until mammography. AJR. 1962 Dec; 88(6):1095-1101.

Clark RL, Copeland MM, Egan RL, Gallager HS, Geller H, Lindsay JP, Robbins LC, White EC. Reproducibility of the technic of mammography (Egan) for cancer of the breast. Am J Surg. 1965 Feb;109:127-133.

Demonstrated that measuring cancer cells circulating in the blood can predict prognoses for patients with advanced breast cancer, thereby helping select those who should be treated aggressively to improve survival.

Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells predict progression free survival and overall survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781-791.

Discovered several abnormal forms of cyclin E, a molecule that controls cell division, in breast cancers with poor response to treatment and poor prognosis; cyclin E is a potential marker for aggressive disease and a target for therapy.

Keyomarsi K, Tucker SL, Buchholz TA, Callister M, Ding Y, Hortobagyi GN, Bedrosian I, Knickerbocker C, Toyofuku W, Lowe M, Herliczek TW, Bacus SS. Cyclin E and survival in patients with breast cancer. N Engl J Med. 2002;347(20):1566-1575. Erratum in: N Engl J Med. 2003;348(2):186.

Discovered persistence of genetic changes related to cancer in the bronchial epithelium of former smokers.

Mao L, Lee JS, Kurie JM, Fan YH, Lippman SM, Lee JJ, Ro JY, Broxson A, Yu R, Morice RC, Kemp BL, Khuri FR, Walsh GL, Hittelman WN, Hong WK. Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst. 1997;89(12):834-836.

Identified a mutation in the kit oncogene that predicts resistance to imatinib (Gleevec), a new agent highly effective against a type of gastrointestinal tumor that expresses kit.

Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W, Raymond AK, Prieto VG, Oyedeji CO, Hunt KK, Pollock RE, Feig BW, Hayes KJ, Choi H, Macapinlac HA, Hittelman W, Velasco MA, Patel S, Burgess MA, Benjamin RS, Frazier ML. A missense mutation in kit kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res. 2004;64(17):5913-5919.

Documented for the first time differences in sensitivity to chemotherapy among different molecular subtypes of breast cancer.

Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, Booser D, Theriault RL, Buzdar AU, Dempsey PJ, Rouzier R, Sneige N, Ross JS, Vidaurre T, Gómez HL, Hortobagyi GN, Pusztai L. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol. 2006;24(26):4236-4244.

Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678-5685.

Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, Kuerer H, Green M, Arun B, Hortobagyi GN, Symmans WF, Pusztai L. Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci U S A. 2005;102(23):8315-8320.

Demonstrated specific biochemical pathways that are blocked by aspirin, celecoxib, and similar agents, which reduce cancer risk.

Shureiqi I, Jiang W, Zuo X, Wu Y, Stimmel JB, Leesnitzer LM, Morris JS, Fan HZ, Fischer SM, Lippman SM. The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells. Proc Natl Acad Sci U S A. 2003;100(17):9968-9973.

Demonstrated that DNA repair genes in smokers who develop bladder cancer are different from those genes in nonsmokers, providing a means of identifying which smokers are at particular risk for cancer.

Wu X, Gu J, Grossman HB, Amos CI, Etzel C, Huang M, Zhang Q, Millikan RE, Lerner S, Dinney CP, Spitz MR. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle–control genes. Am J Hum Genet. 2006;78(3):464-479.

Showed that men who were obese at diagnosis or gained weight at the highest rates were significantly more likely than non-obese men to experience recurrence of prostate cancer after surgery or radiation.

Strom SS, Wang X, Pettaway CA, Logothetis CJ, Yamamura Y, Do KA, Babaian RJ, Troncoso P. Obesity, weight gain and risk of biochemical failure among prostate cancer patients following prostatectomy. Clin Cancer Res. 2005;11(19 Pt 1):6889-6894.

Developed two Bcr-Abl diagnostic tests that can detect and monitor chronic myeloid leukemia and some acute leukemias, thus reducing the need for multiple bone marrow aspirations required for cytogenetic assays that detect the Philadelphia chromosome.

Guo JQ, Lian J, Glassman A, Talpaz M, Kantarjian H, Deisseroth AB, and Arlinghaus RB.
Comparison of Bcr-Abl protein expression and Philadelphia chromosome analysis in chronic myelogenous leukemia patients. American Journal of Clinical Pathology 106:442-448, 1996.

Guo J, Lin H, Kantarjian H, Talpaz M, Champlin R, Andreeff M, Glassman A, and Arlinghaus,RB. Comparison of competitive-nested PCR and real-time PCR in detecting of Bcr-Abl fusion transcripts in chronic myeloid leukemia patients. Leukemia 16:2447-2453, 2002.

Invented a new cryostat for confirming a diagnosis of cancer with “frozen section” pathology slides that could be prepared with greater speed and more clarity while patients remained in surgery.

Chang JP, Russell WO, Moore EB, Sinclair WK. A new cryostat for frozen section technic. Am J Clin Path. 1961; 35(1):14-19.

Developed genomic tests that predict the likelihood of a patient’s breast cancer recurring after surgery without additional treatment and the cancer’s vulnerability to chemotherapy or hormone therapy.

Peintinger F, Anderson K, Mazouni C, Kuerer HM, Hatzis C, Lin F, Hortobagyi GN, Symmans WF, Pusztai L. Thirty-gene pharmacogenomic test correlates with residual cancer burden after preoperative chemotherapy for breast cancer. Clin Cancer Res. 2007;13(14):4078-4082.

Performed the first and the largest case-control study of the relationship between hepatitis B and C viruses and pancreatic cancer, finding that HBV may be a new and possibly preventable risk factor for pancreatic cancer.

Hassan M, Li D, El-Deeb AS, Wolff RA, Bondy ML, Davila M, Abbruzzese JL. Association between hepatitis B virus and pancreatic cancer. J Clin Oncol. 2008;26(28):4557-4562.

Identified methods to utilize oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs, thus possibly sparing patients from more invasive procedures and enabling easier, early detection of lung cancer.

Bhutani M, Pathak AK, Fan Y, Liu D, Lee JJ, Tang H, Kurie JM, Morice RC, Kim ES, Hong WK, Mao L. Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs. Cancer Prev Res. 2008;1:39-44. Commentary: Sidransky D. The oral cavity as a molecular mirror of lung carcinogenesis. Cancer Prev Res. 2008;1:12-14.

Identified two common variations in DNA, known as SNPs, that are strongly associated with lung cancer development. This genome-wide analysis was the first to identify genetic variants that influence lung cancer risk.

Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J, Sullivan K, Matakidou A, Wang Y, Mills G, Doheny K, Tsai YY, Chen WV, Shete S, Spitz MR, Houlston RS (last 2 equal contributors). Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008;40(5):616-622.

Showed that each of three chemotherapy advances for breast cancer were essentially restricted to tumors that were not sensitive to estrogen. Further showed that benefits of chemotherapy were substantial in HER2-positive, estrogen-receptor negative tumors. Conversely, there was no benefit with chemotherapy in tumors that were HER2-negative and estrogen-receptor positive.  

Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L, Hudis C, Winer EP. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006;295:1658 1667.

Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, Broadwater G, Goldstein LJ, Martino S, Ingle JN, Henderson IC, Norton L, Winer EP, Hurdis CA, Ellis MJ, Berry DA. HER2 and response to paclitaxel in node-positive breast cancer. New Engl J Med. 2007;357:1496-1506.

Discovered that human papillomavirus (HPV) status is a strong and independent factor predicting survival among patients treated for head and neck cancer, which suggests that HPV status should be assessed in all patients treated for this common disease.

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363(1):24-35.

Dahlstrom KR, Adler-Storthz K, Etzel CJ, Liu Z, Dillon L, El-Naggar AK, Spitz MR, Schiller JT, Wei Q, Sturgis EM. Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res 2003;9(7):2620-2626.