Journal of Clinical Oncology, Vol 18, Issue 14
(July), 2000: 2728-2732
© 2000 American Society for Clinical Oncology
Occult Ovarian Tumors in Women With BRCA1 or BRCA2 Mutations Undergoing Prophylactic Oophorectomy
By Karen H. Lu,
Judy E. Garber,
Daniel W. Cramer,
William R. Welch,
Jonathan Niloff,
Deborah Schrag,
Ross S. Berkowitz,
Michael G. Muto
From the Familial Ovarian Cancer Center, Cancer Risk and Prevention Program, Division of Cancer Epidemiology and Control, Gillette Center for Women’s Cancers, Dana-Farber Cancer Institute; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, and Department of Pathology, Brigham and Women’s Hospital; and Division of Gynecologic Oncology, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA.
Address reprint requests to Karen H. Lu, MD, Department of Gynecologic Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 67, Houston, TX 77030-4095; email khlu{at}mdanderson.org
 |
ABSTRACT
|
|---|
PURPOSE: To review the findings at prophylactic oophorectomy of a series of women who presented to a familial breast and ovarian cancer clinic.
MATERIALS AND METHODS: Data from medical charts, operative notes, and pathology reports were collected on women who had undergone prophylactic oophorectomies because of the elevated risk of ovarian cancer. Because only a subset of patients underwent BRCA1 and BRCA2 testing, each patient’s risk of hereditary predisposition was calculated using the Berry-Parmigiani model and family history data.
RESULTS: From June 1989 to December 1998, 50 women seen at our clinic underwent prophylactic oophorectomy, 33 of whom had a calculated risk of carrying a germline BRCA1 or BRCA2 mutation greater than 25%. Among this group, four incidental tumors were found (four of 33, or 12%); one tumor was noted at the time of surgery and three were noted only in the final pathology. Two patients had microscopic, poorly differentiated serous adenocarcinomas in multiple sites on both ovaries. A third patient had a bilateral serous borderline tumor with micropapillary features. The fourth patient had a microscopic serous borderline ovarian tumor. All four patients had germline BRCA1 or BRCA2 mutations, and three had unremarkable transvaginal ultrasonography examinations within 6 months before prophylactic surgery.
CONCLUSION: Foci of malignant tumor are not uncommon in prophylactic oophorectomies performed in women at very high risk for ovarian cancer and may not be detected on ultrasonograms. Surgeons should have a high suspicion of finding cancer in these women at the time of prophylactic surgery, and careful pathologic assessment of the specimens should be conducted.
|
INTRODUCTION
|
|---|
WITH THE DISCOVERY of the BRCA1 and BRCA2 genes and the availability of genetic susceptibility testing, we are now able to more accurately define the risk of developing ovarian cancer for an important subset of women. In a woman with a germline BRCA1 mutation, the lifetime risk for ovarian cancer is estimated to be between 20% and 40%.1,2 A germline BRCA2 mutation confers an estimated lifetime risk of ovarian cancer of 10% to 20%.2,3 Strategies for managing this increased risk of ovarian cancer are limited, since the efficacy of screening programs using transvaginal ultrasonography and CA-125 levels remains unproven, and the risk reduction achieved by prophylactic oophorectomy is poorly quantified.4 Nonetheless, prophylactic oophorectomy remains an important option for the prevention of ovarian cancer in women with a strong family history of the disease, and particularly for those with documented BRCA1 and BRCA2 mutations. In this study, we review the findings at prophylactic oophorectomy in our case series of women who presented to a familial breast and ovarian cancer clinic.
|
MATERIALS AND METHODS
|
|---|
A review of all women who were counseled at the combined Dana-Farber Cancer Institute/Brigham and Women’s Hospital Familial Ovarian Cancer and Cancer Risk and Prevention clinics and who subsequently underwent prophylactic oophorectomy was conducted. Prophylactic surgery was strictly defined: the indication for surgery had to have been for prophylaxis only and excluded surgical patients who had a CA-125 level greater than 34 U/mL or any ovarian abnormality seen on preoperative ultrasonograms.
Over the 10-year period from 1989 to 1998, the definition of a woman at high risk for ovarian cancer evolved. During the initial years of the clinics, surgery was generally offered to women with two primary relatives with histologically confirmed epithelial ovarian cancer. Some women with a single primary relative who had developed ovarian cancer at a young age were also offered prophylactic surgery. Recent advances have permitted more objective assessments. Genetic susceptibility testing for BRCA1 and BRCA2 mutations has been introduced as well as formal models for estimating the a priori probability of carrying a germline mutation. The Berry-Parmigiani model, BRCAPRO, calculates an individual’s risk of carrying a germline BRCA1 or BRCA2 mutation based on family history of ovarian or breast cancer, age at diagnosis for each family member, and ethnicity.5
Twenty women underwent preoperative BRCA1 and BRCA2 testing in protocols approved by our institutional review boards. Any patient subsequently identified as having an occult cancer was offered BRCA1 or BRCA2 testing unless it had already been performed preoperatively. Because our series included patients whose surgery occurred before the availability of genetic testing and patients who elected not to undergo testing, each patient in the study had BRCAPRO scores determined from collected pedigrees. Medical record confirmation of the diagnosis of epithelial ovarian cancer in family members was obtained.
Surgical and clinical data were abstracted from clinic and hospital charts. In the majority of cases (37 of 50), ovaries and fallopian tubes were entirely sectioned (2- to 3-mm intervals) and submitted in toto for microscopic evaluation. In cases in which surgery was performed at outside institutions (13 of 50), ovaries and fallopian tubes were not entirely sectioned. However, all available slides were requested and reviewed by a single gynecologic pathologist (W.R.W.).
|
RESULTS
|
|---|
The mean age at the time of surgery was 46.0 years for the 50 women who had undergone prophylactic surgery (range, 31 to 65 years). Of the 50 women, 33 had a greater than 25% risk of carrying a germline BRCA1 or BRCA2 mutation, including all 19 patients known preoperatively to carry a mutation and one patient who was found to have a mutation of uncertain significance. Two women had a 10% to 25% risk of carrying a mutation, and 15 women had a less than 10% risk of carrying a mutation (Table 1).
Thirty-seven of the 50 women had undergone transvaginal ultrasonography within the 6 months before surgery; six others had transvaginal ultrasonography performed 6 to 13 months before surgery. Ultrasonography data were unknown for seven patients. CA-125 data were not available for the majority of our patients, because it is not our practice to track CA-125 levels in premenopausal patients due to the high false-positive rate.
Twelve women had received laparoscopic bilateral salpingo-oophorectomies and 38 had received laparotomies. Thirty-four of the 50 women had elected to have concurrent hysterectomies. Four gynecologic oncologists performed 37 of the surgeries. The other 13 surgeries were performed by 12 different gynecologists. There were no surgical complications.
Four women were found to have ovarian neoplasms (Fig 1); one was detected at the time of surgery and three were found during detailed histologic evaluation. All four of these women were identified from the group with pedigrees that conferred a greater than 25% probability of carrying a germline BRCA1 or BRCA2 mutation. Only one patient was known preoperatively to carry a BRCA1 mutation. The three other patients were offered and elected to undergo testing after their surgeries. Two patients were found to have BRCA1 mutations and one patient had a BRCA2 mutation. Three of the women had normal transvaginal ultrasonograms within 6 months before their surgery, and one woman had a normal ultrasonogram 11 months before surgery.
View larger version (153K):
[in this window]
[in a new window]
|
Fig 1. Photomicrograph of tumors found in four high-risk women who underwent prophylactic oophorectomy: (a) patient no. 1, (b) patient no. 2, (c) patient no. 3, (d) patient no. 4. Abbreviations: T, tumor; Ov, ovary; FT, fallopian tube.
|
|
Clinical and histologic data on these four patients are listed in Table 2. Patient no. 1 was a 49-year-old woman with a BRCA1 mutation. No abnormalities were seen at the time of surgery. However, at the time of histologic review, multiple 1-mm foci of grade 3 serous adenocarcinoma were present on the surfaces of the right and left ovaries and left fallopian tube. This case likely represents an early serous surface carcinoma. Patient no. 2 was a 65-year-old woman with a BRCA2 mutation who had undergone a laparoscopic bilateral salpingo-oophorectomy. In addition to a normal transvaginal ultrasonogram, the patient had a CA-125 level of less than 8 U/mL 11 months before surgery. While no abnormalities were seen at the time of surgery, pathologists noted grade 3 serous adenocarcinoma in a 2-mm loose fragment of tissue adjacent to the right fallopian tube as well as microscopic implants of carcinoma on the ovarian surface and within paraovarian adhesions. At staging laparotomy 20 days after her initial laparoscopic procedure, multiple 6- to 8-mm peritoneal implants of grade 3 serous adenocarcinoma were noted in the right and left paracolic gutters. Patient no. 3 was a 40-year-old woman with a BRCA1 mutation. During surgery, the ovaries were noted to be normal in size. However, multiple, distinct, 8- to 10-mm nodules were seen on both ovaries. No other sites of tumor were seen beyond the ovaries. Frozen section indicated a probable serous borderline tumor. Final pathology revealed a serous borderline tumor with unusual features, including micropapillary growth and significant cytologic atypia. Patient no. 4 was a 49-year-old woman with a BRCA1 mutation and a history of breast cancer. She had normal-appearing ovaries and tubes at the time of surgery, but a microscopic, intracystic, serous borderline ovarian tumor was found in the left ovary on histologic review.
|
DISCUSSION
|
|---|
Of 33 women with a high calculated risk of carrying a BRCA1 or BRCA2 mutation, four (12%) were found to have microscopic or very small ovarian tumors, three of which were detected only by detailed histologic evaluation. All four patients carried germline BRCA1 or BRCA2 mutations, but only one was known preoperatively to carry a mutation (BRCA1). Three of the women had normal transvaginal ultrasonograms within 6 months before their surgery, and one had a normal transvaginal ultrasonogram and a normal CA-125 level 11 months before surgery. Clearly, annual screening was not helpful in detecting early ovarian cancer in this high-risk group. No occult cancers were found in the 15 patients with unknown mutation status who had a low probability (< 10%) of carrying a BRCA1 or BRCA2 mutation. The majority of these women had undergone surgery in the early years of the study when we were less able to define a patient’s hereditary risk for ovarian cancer. We currently would not recommend prophylactic surgery for this subgroup.
Occult ovarian malignancies have been reported by other investigators. Salazar et al6 reviewed the histology of ovaries removed for prophylaxis from 20 women with a strong family history for ovarian cancer. He found two patients with microscopic adenocarcinomas (two of 20, or 10%), one of whom was known to carry a germline BRCA1 mutation. Johannsson et al7 reported on a series of Swedish families with germline BRCA1 mutations in which two (25%) of eight women who underwent prophylactic oophorectomies were found to have ovarian cancer at the time of surgery. The results of these studies and ours suggest that women with BRCA1 or BRCA2 mutations have a substantial risk of early ovarian cancer being found at the time of prophylactic surgery.
In our study, three of the four incidental tumors were undetectable by gross examination and could have been missed if only representative sections had been submitted for histologic evaluation. We believe that representative sampling of specimens from these patients by the pathologist is insufficient. Chen et al8 reported a case of a patient with a strong family history of ovarian cancer who developed papillary serous carcinoma of the peritoneum (PSCP) several years after prophylactic oophorectomy. In serial sections of the specimen performed retrospectively, a microscopic focus of adenocarcinoma on the surface of the ovary was found. We recommend that when prophylactic surgery specimens are obtained, pathologists section and histologically examine ovaries and fallopian tubes in toto. Even when the ovaries and fallopian tubes from these high-risk women are grossly normal-appearing, small foci of tumor may be found after detailed histologic review.
In one of the occult tumor cases in this series, re-exploration after initial laparoscopy revealed multiple implants on the peritoneal surfaces of the abdomen. This case likely represents an early PSCP. We and others have shown that patients with BRCA1 or BRCA2 mutations may develop multifocal PSCP.9,10 A second patient had a microscopic serous carcinoma confined to the surfaces of the right and left ovary and left fallopian tube. The presentation of these two cases is noteworthy for the surface tumors on the ovaries and peritoneum rather than tumor in the ovarian parenchyma. In addition, these two cases illustrate that in patients with BRCA1 and BRCA2 mutations, disease may be present, at even the earliest stages, in multiple locations on ovaries, fallopian tubes, and peritoneal surfaces.
Two of our patients with incidental tumors were found to have borderline ovarian tumors. One patient presented with multiple, distinct foci of tumor on the surfaces of both ovaries. Despite the fact that the foci of tumor were each approximately 1 cm in diameter, review of the preoperative ultrasonogram did not reveal any abnormalities. The final histology of this tumor revealed a papillary serous borderline tumor with unusual features, including micropapillary growth and significant cytologic atypia. This particular case may represent an early precursor to invasive ovarian cancer. The second borderline tumor was a microscopic focus of serous borderline tumor in one ovary. These cases raise questions as to whether borderline tumors should be considered as components of the hereditary breast and ovarian cancer syndrome. Although individual cases of borderline tumors have been reported in patients with germline BRCA1 mutations, our group and others have found that these tumors are less frequently associated with germline BRCA1 or BRCA2 mutations.11,12
None of our patients who had normal ovaries and tubes have subsequently developed PSCP, but a longer follow-up period is needed before we can draw conclusions about the risk of PSCP after prophylactic oophorectomy. We counsel patients before prophylactic oophorectomy about the potential risk of PSCP,13,14 and we observe patients after surgery with yearly physical examinations and assessments of CA-125 levels. Long-term follow-up of this group of women is ongoing so that we can obtain further information about the efficacy of prophylactic surgery, the consequences of early surgical menopause, and overall patient satisfaction.
In addition to the reduction in ovarian cancer risk, Rebbeck et al15 recently reported a reduction in breast cancer risk after prophylactic oophorectomy in women with germline BRCA1 mutations.15 More women who carry germline BRCA1 and BRCA2 mutations may choose to undergo prophylactic oophorectomy to decrease their risk of ovarian and breast cancer. Given our experience, we propose the following recommendations for surgeons performing prophylactic oophorectomy in these high-risk women. In addition to the potential risk of developing PSCP after prophylactic oophorectomy, the preoperative counseling should discuss the possibility of finding an occult malignancy and the extent of surgery should a cancer be found. At the time of prophylactic surgery, a thorough examination of the pelvis, upper abdomen, paracolic gutters, and bowel should be performed. Care should be taken to remove ovaries and fallopian tubes in their entirety, whether the surgery is performed by laparotomy or laparoscopy. We also recommend obtaining pelvic washings, an omental biopsy, and a Pap smear of the diaphragm. Finally, pathologists should be alerted to the need for exhaustive histologic evaluation of ovaries, tubes, and peritoneal specimens from these patients. Even normal-appearing ovaries and fallopian tubes removed from these genetically high-risk women may harbor occult foci of carcinoma.
|
ACKNOWLEDGMENTS
|
|---|
We thank Anu Chittendon for her assistance in calculating Berry-Parmigiani scores for the cohort.
|
REFERENCES
|
|---|
1.
Ford D, Easton DF, Bishop DT, et al: Risks of cancer in BRCA1 mutation carriers. Lancet 343:692-695, 1994[Medline]
2.
Struewing JP, Hartge P, Wacholder S, et al: The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401-1408, 1997[Abstract/Free Full Text]
3.
Ford D, Easton DF, Stratton M, et al: Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62:676-689, 1998[Medline]
4.
Muto MG, Cramer DW, Brown DL, et al: Screening for ovarian cancer: The preliminary experience of a familial ovarian cancer center. Gynecol Oncol 51:12-20, 1993[Medline]
5.
Parmigiani G, Berry DA, Aguilar O: Determining carrier probabilities for breast cancer susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 62:145-158, 1998[Medline]
6.
Salazar H, Godwin AK, Daly MB, et al: Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies. J Natl Cancer Inst 88:1810-1820, 1996[Abstract/Free Full Text]
7.
Johannsson OT, Ranstam J, Borg A, et al: Survival of BRCA1 breast and ovarian cancer patients: A population-based study from southern Sweden. J Clin Oncol 16:397-404, 1998[Abstract]
8.
Chen KT, Schooley JL, Flam MS: Peritoneal carcinomatosis after prophylactic oophorectomy in familial ovarian cancer syndrome. Obstet Gynecol 66:93S–94S, 1985 (suppl)
9.
Schorge JO, Muto MG, Welch WR, et al: Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCA1 mutations. J Natl Cancer Inst 90:841-845, 1998[Abstract/Free Full Text]
10.
Karlan BY, Baldwin RL, Lopez-Luevanos E, et al: Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: Implications for ovarian cancer screening. Am J Obstet Gynecol 180:917-928, 1999[Medline]
11.
Lu KH, Cramer DW, Muto MG, et al: A population-based study of BRCA1 and BRCA2 mutations in Jewish women with epithelial ovarian cancer. Obstet Gynecol 93:34-37, 1999[Abstract/Free Full Text]
12.
Gotlieb WH, Friedman E, Bar-Sade RB, et al: Rates of Jewish ancestral mutations in BRCA1 and BRCA2 in borderline ovarian tumors. J Natl Cancer Inst 90:995-1000, 1998[Abstract/Free Full Text]
13.
Piver MS, Jishi MF, Tsukada Y, et al: Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer: A report of the Gilda Radner Familial Ovarian Cancer Registry. Cancer 71:2751-2755, 1993[Medline]
14.
Tobacman JK, Greene MH, Tucker MA, et al: Intra-abdominal carcinomatosis after prophylactic oophorectomy in ovarian cancer prone families. Lancet 2:795-797, 1982[Medline]
15.
Rebbeck TR, Levin AM, Eisen A, et al: Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 91:1475-1479, 1999[Abstract/Free Full Text]
Submitted August 17, 1999;
accepted March 14, 2000.
This article has been cited by other articles:
|
|
|
|
 
K. Levanon, C. Crum, and R. Drapkin
New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact
J. Clin. Oncol.,
November 10, 2008;
26(32):
5284 - 5293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Greene, M. Piedmonte, D. Alberts, M. Gail, M. Hensley, Z. Miner, P. L. Mai, J. Loud, G. Rodriguez, J. Basil, et al.
A Prospective Study of Risk-Reducing Salpingo-oophorectomy and Longitudinal CA-125 Screening among Women at Increased Genetic Risk of Ovarian Cancer: Design and Baseline Characteristics: A Gynecologic Oncology Group Study
Cancer Epidemiol. Biomarkers Prev.,
March 1, 2008;
17(3):
594 - 604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Callahan, C. P. Crum, F. Medeiros, D. W. Kindelberger, J. A. Elvin, J. E. Garber, C. M. Feltmate, R. S. Berkowitz, and M. G. Muto
Primary Fallopian Tube Malignancies in BRCA-Positive Women Undergoing Surgery for Ovarian Cancer Risk Reduction
J. Clin. Oncol.,
September 1, 2007;
25(25):
3985 - 3990.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. D. Kauff and R. R. Barakat
Risk-Reducing Salpingo-Oophorectomy in Patients With Germline Mutations in BRCA1 or BRCA2
J. Clin. Oncol.,
July 10, 2007;
25(20):
2921 - 2927.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-m. Chen, K. Y. Yang, S. E. Little, M. K. Cheung, and A. B. Caughey
Gynecologic Cancer Prevention in Lynch Syndrome/Hereditary Nonpolyposis Colorectal Cancer Families
Obstet. Gynecol.,
July 1, 2007;
110(1):
18 - 25.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Y. Karlan, A. Berchuck, and D. Mutch
The Role of Genetic Testing for Cancer Susceptibility in Gynecologic Practice
Obstet. Gynecol.,
July 1, 2007;
110(1):
155 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Guillem, W. C. Wood, J. F. Moley, A. Berchuck, B. Y. Karlan, D. G. Mutch, R. F. Gagel, J. Weitzel, M. Morrow, B. L. Weber, et al.
ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes
J. Clin. Oncol.,
October 1, 2006;
24(28):
4642 - 4660.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Guillem, W. C. Wood, J. F. Moley, A. Berchuck, B. Y. Karlan, D. G. Mutch, R. F. Gagel, J. Weitzel, M. Morrow, B. L. Weber, et al.
ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes
Ann. Surg. Oncol.,
October 1, 2006;
13(10):
1296 - 1321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Schmeler, C. C. Sun, D. C. Bodurka, K. G. White, P. T. Soliman, A. R. Uyei, J. L. Erlichman, B. K. Arun, M. S. Daniels, S. A. Rimes, et al.
Prophylactic Bilateral Salpingo-Oophorectomy Compared With Surveillance in Women With BRCA Mutations.
Obstet. Gynecol.,
September 1, 2006;
108(3):
515 - 520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Brewer, J. Ranger-Moore, A. Baruche, D. S. Alberts, M. Greene, D. Thompson, Y. Liu, J. Davis, and P. H. Bartels
Exploratory Study of Ovarian Intraepithelial Neoplasia
Cancer Epidemiol. Biomarkers Prev.,
February 1, 2005;
14(2):
299 - 305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. B. Powell, E. Kenley, L.-m. Chen, B. Crawford, J. McLennan, C. Zaloudek, M. Komaromy, M. Beattie, and J. Ziegler
Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers: Role of Serial Sectioning in the Detection of Occult Malignancy
J. Clin. Oncol.,
January 1, 2005;
23(1):
127 - 132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Hogg and M. Friedlander
Biology of Epithelial Ovarian Cancer: Implications for Screening Women at High Genetic Risk
J. Clin. Oncol.,
April 1, 2004;
22(7):
1315 - 1327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Chung, R. Broaddus, M. Crozier, R. Luthraa, C. Levenback, and K. Lu
Unexpected Endometrial Cancer at Prophylactic Hysterectomy in a Woman With Hereditary Nonpolyposis Colon Cancer
Obstet. Gynecol.,
November 1, 2003;
102(5):
1152 - 1155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Brewer, K. Johnson, M. Follen, D. Gershenson, and R. Bast Jr.
Prevention of Ovarian Cancer: Intraepithelial Neoplasia
Clin. Cancer Res.,
January 1, 2003;
9(1):
20 - 30.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. UDAGAWA, A. FERNANDEZ, E.-G. ACHILLES, J. FOLKMAN, and R. J. D'AMATO
Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy
FASEB J,
September 1, 2002;
16(11):
1361 - 1370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. DeMichele and B. L. Weber
Risk Management in BRCA1 and BRCA2 Mutation Carriers: Lessons Learned, Challenges Posed
J. Clin. Oncol.,
March 1, 2002;
20(5):
1164 - 1166.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Scheuer, N. Kauff, M. Robson, B. Kelly, R. Barakat, J. Satagopan, N. Ellis, M. Hensley, J. Boyd, P. Borgen, et al.
Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers
J. Clin. Oncol.,
March 1, 2002;
20(5):
1260 - 1268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brewer, U. Utzinger, W. Satterfield, L. Hill, D. Gershenson, R. Bast, J. T. Wharton, R. Richards-Kortum, and M. Follen
Biomarker Modulation in a Nonhuman Rhesus Primate Model for Ovarian Cancer Chemoprevention
Cancer Epidemiol. Biomarkers Prev.,
August 1, 2001;
10(8):
889 - 893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Weitzel and L. E. McCahill
The Power of Genetics to Target Surgical Prevention
N. Engl. J. Med.,
June 21, 2001;
344(25):
1942 - 1944.
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
