Publications by authors named "Gemma B Uy"

10 Publications

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Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

J Natl Cancer Inst 2015 Jun 19;107(6):djv064. Epub 2015 Mar 19.

International Breast Cancer Research Foundation, Madison, WI (RRL); University of the Philippines Manila, Philippine General Hospital, Manila, Philippines (AL, GU, ADP, RD, OB); Hospital K, Hanoi, Vietnam (NVD, LHQ, NDL, TVT); Clarient Pathology Services, Aliso Viejo, CA (DCA); East Avenue Medical Center, Manila, Philippines (JS); Vicente Sotto Hospital, Cebu, Philippines (SSS); Rizal Medical Center, Manila, Philippines (RML, MHA); Hue Central Hospital, Hue, Vietnam (NDT); National Institute of Oncology, Rabat, Morocco (NB); Santo Tomas University Hospital, Manila, Philippines (NN); Danang General Hospital, Danang, Vietnam (TTQ); The Ohio State University Center for Biostatistics, Columbus, OH (GSY, EMH, DJ (ret.).

Background: For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes.

Methods: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided.

Results: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses.

Conclusions: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.
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June 2015

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer.

Cancer 2013 Nov 20;119(21):3746-52. Epub 2013 Aug 20.

International Breast Cancer Research Foundation, Madison, Wisconsin.

Background: In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described.

Methods: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies.

Results: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first 12 months (P < .0001) and then began to stabilize.

Conclusions: Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck.
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November 2013

CYP2D6 genotypes, endoxifen levels, and disease recurrence in 224 Filipino and Vietnamese women receiving adjuvant tamoxifen for operable breast cancer.

Springerplus 2013 Dec 15;2(1):52. Epub 2013 Feb 15.

International Breast Cancer Research Foundation, 505 S Rosa Rd Ste 35E, Madison, WI 53719 USA.

Background: While tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results.

Findings: In an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case-control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease. We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control.

Conclusions: This exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70, endoxifen may promote recurrence.
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December 2013

A randomized, double-blinded placebo-controlled clinical trial of the routine use of preoperative antibiotic prophylaxis in modified radical mastectomy.

World J Surg 2013 Jan;37(1):59-66

Department of Surgery, University of the Philippines Manila-Philippine General Hospital, Taft Avenue, 1000 Manila, Philippines.

Background: The effectiveness of antibiotic prophylaxis for prevention of surgical site infection (SSI) following specific types of breast cancer surgery remains uncertain. This study assessed the effectiveness of prophylaxis in modified radical mastectomy (MRM).

Methods: Women undergoing MRM for breast cancer were recruited. Women were excluded who had diabetes mellitus, severe malnutrition or known allergy to cephalosporins; were receiving corticosteroid therapy or were treated with antibiotics within one week prior to surgery; were scheduled for simultaneous breast reconstruction or bilateral oophorectomy; had existing local infection. Participants were randomized to receive either intravenous cefazolin 1 g or placebo within 30 min prior to skin incision. Standard skin preparation and operative technique for MRM were carried out. Wounds were assessed for SSI and other complications weekly for 30 days.

Results: A total of 254 women were recruited. Age, clinical stage, prior chemotherapy, and operative time were similar for antibiotic and placebo groups. The overall incidence of SSI was 14.2 %. There were no significant differences in the infection rate over the 30-day follow-up period between the placebo and antibiotic groups (15 % vs 13.4 %; p = 0.719) or at each week. The majority of SSI were either cellulitis or superficial infection for both groups. There were no significant differences between groups in treatments required for SSI, incidence of hematoma or seroma.

Conclusions: The findings of this study, alone and when meta-analyzed with data from studies in similar surgical populations, do not support the use of antibiotic prophylaxis in MRM.
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January 2013

Cancer incidence and survival in Metro Manila and Rizal province, Philippines.

Jpn J Clin Oncol 2010 Jul 12;40(7):603-12. Epub 2010 Apr 12.

Department of Surgery, University of the Philippines Manila, Philippine General Hospital, Manila, Philippines.

The database of two population-based cancer registries (Philippine Cancer Society-Manila Cancer Registry and Department of Health-Rizal Cancer Registry) was used to generate age-standardized incidence rates of cancer during 1980-2002. Five-year relative survival rates were obtained for incident cases from 1993 to 2002 using a period analysis method. Overall incidence had increased in both males and females. Among males, lung cancer was the leading cancer and reached a peak in 1988-92. Colorectal and prostate cancers showed rising trends and became more common than liver cancer, with stable incidence over time. Stomach cancer incidence fell steeply. Among females, there was a steady increase in incidence of breast cancer. There was a slight decrease in the incidence of the second common cancer, cervical cancer, and colorectal cancer became equally common. Lung cancer incidence in females also reached a peak by 1998-2002 and then slightly decreased. Oral cavity cancer decreased strongly in the last period. In general, survival rates among Philippine residents were one-third lower than among Filipino-Americans and Whites in the USA especially in cancer sites wherein effective early detection methods may be available such as breast, cervix, colorectal and thyroid cancers. Survival was also lower in Philippine leukemia cases, a disease wherein effective treatment is proven in some types but is quite expensive. Lifestyle factors such as smoking, unhealthy diet, physical inactivity, and human papillomavirus and hepatitis B virus infections were associated with some incidence patterns. Late stage at diagnosis was largely responsible for low survival.
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July 2010

Breast cancer hormone receptor assay results of core needle biopsy and modified radical mastectomy specimens from the same patients.

Clin Breast Cancer 2010 Apr;10(2):154-9

Department of Surgery, Philippine General Hospital, University of the Philippines, Manila, Philippine.

Background: Hormone receptor (HR) expression is the most important biomarker and is the cornerstone in the management of breast cancer. Therefore, the accuracy of its testing is critical in treatment decisions.

Patients And Methods: A total of 160 consecutive patients accrued to an adjuvant hormonal therapy clinical trial between March 2003 and May 2008 were studied. Estrogen receptor (ER) and progesterone receptor (PgR) protein assays of tissues from modified radical mastectomy (MRM) specimens were compared with their previous core needle biopsy (CNB) ER and PgR immunohistochemical assay results.

Results: The tumors of 146 (91.2%) out of the 160 patients with CNB HR-positive disease remained HR positive in MRM specimen assays. Estrogen receptor positivity decreased from 95% in the CNB to 81.9% in MRM specimens and PgR positivity from 93.8% to 86.9%. The overall agreement between CNB and MRM specimens was 81.9% for ER and 85.6% for PgR. The mean Allred scores were significantly higher in CNB than in MRM specimens: ER, 6.6 (SD, 2.02) versus 4.71 (SD, 2.62); PgR, 6.68 (SD, 2.16) versus 5.99 (SD, 2.68); P < .001 and P = .001, respectively.

Conclusion: Core needle biopsy specimens are associated with the identification of more frequent and higher levels of tumoral hormonal receptor proteins than MRM specimens. Delayed fixation of MRM tissues likely accounted for this finding. Optimal selection of patients for hormonal therapies is dependent on tissue management strategies before formal hormonal receptor protein testing procedures.
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April 2010

Epidemiology and clinicopathology of breast cancer in metro Manila and Rizal Province, Philippines.

Asian Pac J Cancer Prev 2009 Jan-Mar;10(1):167-72

Dept of Surgery, Philippine General Hospital, University of the Philippines/Philippine Cancer Society-Manila Cancer Registry, Manila, Philippines.

The breast cancer incidence in the Philippines is among the highest in Asia. Age-standardized incidence rates (ASR) in Metro Manila and Rizal Province derived from the Philippine Cancer Society-Manila Cancer Registry and the Department of Health-Rizal Cancer Registry showed increase from 1980 to 2002, and were significantly higher in 7 cities in Metro Manila and significantly lower in 14 cities/municipalities mostly in Rizal Province. The AJCC Clinical Stage did not change from 1993 to 2002 among incident cases, the average distribution being: I= 5%, IIA= 20%, IIB= 18%, IIIA= 9%, IIIB= 10%, IV= 11%, Unknown= 28%. The International Agency for Research on Cancer attempted to run a randomized screening trial in 1995-1997 in the Philippines based on clinical breast examination by trained nurses and midwives. Unfortunately, even after home visits by a team equipped to perform needle biopsy, only 35% of screen-positive cases eventually had a diagnostic test. The estimated prevalence of BRCA mutations among unselected patients in the Philippine General Hospital (PGH) in 1998 was 5.1%, with a prevalence of 4.1% for BRCA2 mutations alone. There is a continuing effort at improving IHC hormone receptor testing at PGH, particularly on early fixation in buffered formalin. It was observed that hormone receptor-positive proportions tended to be higher in core needle biopsy specimens (72%) compared to mastectomy specimens (65%). During the years 1991, 1994 and 1997, 97% of incident cases of early breast cancer underwent modified radical mastectomy, 18% had postoperative radiotherapy, 51% had adjuvant hormone treatment and 47% received adjuvant chemotherapy. Survival of incident cases in 1993 to 2002 was compared to that of Filipino-Americans and Caucasians in the SEER 13 database. The age-adjusted 5-year relative survival, using period analysis, of Metro Manila residents, Filipino-Americans and Caucasians were 58.6%, 89.6% and 88.3% respectively.
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August 2009

Surgical oophorectomy for breast cancer: back to the future.

Future Oncol 2008 Dec;4(6):785-92

Ohio State University Comprehensive Cancer Center, B402 Starling Loving Hall, 302 W, 10th Ave, Columbus, OH 43210, USA.

While the preponderance of current scientific presentations on breast cancer therapies has focused on chemotherapeutic strategies, targeted therapy with tyrosine kinase inhibitors and hormonal therapies for postmenopausal women, the majority of worldwide cases of breast cancer occur in premenopausal women, for whom practical inexpensive hormonal therapy, surgical oophorectomy, is the most common attainable treatment. In hormone-receptor-positive breast cancer, meta-analysis data from older trials, and more specific recent trial data have made clearer the chronic natural history of this broad subtype of disease and the central role of hormonal therapy in its control. Greater understanding of the critical variables in pathology procedures for breast tumor tissue hormonal receptor testing is leading to better definitions of the specific patients for whom hormonal therapies are indicated. Closer examination of outcomes following surgical oophorectomy has suggested that more than just downregulation of estrogen stimulated breast cancer growth; the reduction of systemic estrogen levels also occurs with this procedure. When combined with antiestrogen treatment using tamoxifen in patients who are active metabolizers of this drug, surgical oophorectomy is a remarkably effective and cost-effective treatment. This combination of circumstances suggests that this first hormonal therapy for breast cancer may once again, have a much greater role globally.
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December 2008

Clinical and molecular biologic characteristics of early-onset versus late-onset colorectal carcinoma in Filipinos.

World J Surg 2004 Feb 8;28(2):117-23. Epub 2004 Jan 8.

Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 29814-4799, USA.

A case-control study of Filipino patients who underwent surgical resection for colorectal cancer (CRC) during a 1-year period was undertaken. Thirty-five patients under age 40 years were identified. Paraffin blocks of these and 35 randomly selected patients over age 40 underwent histologic and immunohistochemical evaluation. Markers chosen for evaluation included the apoptosis-associated gene products (p53 and bcl-2), a tumor proliferation activity-related factor (Ki-67), and the markers (MLH1 and MSH2) of DNA microsatellite instability (MSI). Results were correlated with age and the stage and location of the tumor. The average age of the early-onset group was 30.7 years compared to the late-onset group at 67.0 years; and the male/female ratio was equivalent. The younger patients had a significantly higher Dukes' stage, the tumors were more poorly differentiated, and they were more frequently of the mucinous and signet ring cell histopathologic type. Expression of p53 was higher in the younger patients ( p < 0.001) and was independent of the degree of differentiation or the stage of the tumor. No differences of expression were noted for the other markers measured. The increased frequency of CRC in Filipino patients less than 40 years of age offers a unique opportunity to gain a better understanding of carcinogenesis, which might be exploited during diagnosis and management. The differences noted between the early- and late-onset CRC are provocative and provide an impetus for increased screening in Filipinos.
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February 2004

Comparative analysis of hemostatic agents in a swine model of lethal groin injury.

J Trauma 2003 Jun;54(6):1077-82

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.

Background: Techniques for better hemorrhage control after injury could change outcome. A large-animal model of lethal, uncontrolled hemorrhage was developed to test whether the use of various hemostatic agents would decrease bleeding and improve early survival.

Methods: A complex groin injury was created in 30 Yorkshire swine (42-55 kg) to produce uncontrolled hemorrhage. This injury included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 5 minutes, the animals were randomized to (n = 6 animals per group) no dressing (ND), standard dressing (SD), SD and Rapid Deployment Hemostat (RDH) bandage, SD and QuikClot hemostatic agent (QC), or SD and TraumaDEX (TDEX). Limited volume 0.9% saline (1,000 mL over 30 minutes) resuscitation was started 30 minutes after injury. We measured blood loss, early mortality (180 minutes), and physiologic markers of hemorrhagic shock (e.g., cardiac output, blood pressure, hemoglobin, metabolic acidosis).

Results: Application of wound dressing decreased mortality in all groups compared with the ND group (83% mortality). However, this difference was significant (p < 0.05) only for the QuikClot hemostatic agent (0% mortality). Before the application of dressing (first 5 minutes), there were no differences in blood loss between the groups. After application of dressings, the QC group had the lowest blood loss (4.4 +/- 1.4 mL/kg).

Conclusion: Of the hemostatic agents tested, QuikClot improved survival and decreased bleeding in a swine model of lethal vascular and soft tissue injury.
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June 2003