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Parity, age at first childbirth, and risk of ovarian cancer
Citations from the literature /International
Journal of Gynecology & Obstetrics 50 (1995) 111-121
linear analysis, persisted within each severity stratum of cervical intraepithelial neoplasia and was independent of associated human papillomavirus infection. In human immunodeficiency virus-positive patients log-linear analysis showed that highgrade cervical intraepithelial neoplasia, the presence of human papillomavirus infection, and the severity of human immunodeficiency virus disease were independently correlated with increased nucleolar organizer regions-associated protein counts per cell. Conclusion: The results of this study indicate that the proliferative activity of cervical intraepithelial neoplasia lesions of human immunodeficiency virus-positive patients was increased compared with matched lesions from human immunodeficiency virus-negative women. This finding suggests the possibility of an increased oncogenic progression of cervical intraepithelial neoplasia lesions in human immunodeliciency virus-positive patients. Development of endometrial cancer in women on estrogen and progestin hormone replacement therapy McGonigle K.F.; Karlan B.Y.; Barbuto D.A.; Leuchter R.S.; Lagasse L.D.; Judd H.L. USA GYNECOL. ONCOL. 1994 5511 (126-132) The presenting symptoms, hormonal regimens, treatment modalities, tumor pathology, and follow-up of 25 women developing endometrial cancer while receiving postmenopausal estrogen and progestin therapy were investigated retrospectively. Patients were interviewed and hormone therapies were confirmed through medical records. Pathology specimens were reviewed. Patients received conjugated estrogens (n = 20) or another estrogen (n = 5). For those on conjugated estrogens, the mean daily dose was 0.68 mg, monthly duration was 24.9 days, and monthly dose was 17.0 mg. Women also received medroxyprogesterone acetate (n = 23) or norethindrone acetate (n = 2). The most common regimen was sequential medroxyprogesterone acetate, at a mean daily dose of 7.5 mg, monthly duration of 9.3 days, and monthly dose of 68 mg (mean duration=5.7 years). Most tumors were low stage and grade, with few demonstrating grade 3 disease (n = 2) or greater than 50% myometrial invasion (n = 2). Twenty-three (92%) had disease limited to the uterus, while two had stage IIIA disease. All are alive and disease-free after a median follow-up of 26 months. Estrogen and progestin therapy does not prevent endometrial cancer in all patients. Women who developed this tumor on sequential therapy in general received less than the recommended guidelines for daily dosage and monthly duration of progestin. Most patients had early-stage and low-grade disease. Continued vigilance in the care of women on hormone replacement therapy is necessary even when combination therapy is prescribed. Factors contributing to the accuracy in diagnosing ovarian malignancy by color doppler ultrasound Wu C-C.; Lee C.-N.; Chen T.-M.; Lai J.-I.; Hsieh C.-Y.; Hsieh F.-J. TWN OBSTET. GYNECOL. 1994 84/4 I (605-608) Objective: To determine whether resistance index values ob-
113
tained by color Doppler ultrasound contribute to the accuracy in diagnosing ovarian malignancies. Methods: Four hundred ten patients with ovarian neoplasms referred for color Doppler ultrasound evaluation were enrolled, excluding patients examined during the luteal phase. Resistance index of the intratumor arteries was measured by color Doppler ultrasound. The corresponding clinical and histopathologic information was recorded. For statistical determinations, we used the Yates corrected chi2 analysis, Fisher exact test, Student f test. and linear regression analysis. Results: Satisfactory intra-tumor artery waveforms were obtained in 96.1% (99 of 103) of ovarian malignancies. Resistance index values varied at 0.23-0.82. Regression analysis of resistance index values on tumor size and amount of ascites demonstrated a linear association (R=0.498 and 0.362, respectively; P < 0.01 in both). If we regard a resistance index of 0.4 as a cutoff value, the overall sensitivity and specificity in detecting malignancy were 68.0 and 97.4%. respectively. Primary ovarian malignancies exhibited signilicantly more false negatives (30 of 79) than malignancies metastasized to the ovary (three of 24) (P = 0.018). Malignancies containing mainly cystic components exhibited more false negatives (20 of 41) than did tumors with primarily solid components (I3 of 62) (P < 0.01). Significantly more false negatives were encountered in malignancies with larger diameters (greater than IO cm) compared to smaller ones (27 of 63 vs. six of 40; P < O.Ol), and in malignancies accompanied by considerable ascites (greater than 1000 ml) (I 3 of 25 vs. 20 of 78; P < 0.05). Conclusions: Tumor origin, size, component nature, and amount of ascites contributed to the accuracy in diagnosing ovarian malignancies using resistance index values obtained by color Doppler ultrasound. Parity, age at fist childbirth, and risk of ovarian cancer Adami H.-O.; Hsieh C-C.; Lambe M.; Trichopoulos D.; Leon D.; Persson I.; Ekbom A.; Janson P.O. SWE LANCET 1994 344/8932 ( l250- 1254) Increasing parity is associated with a reduction in the risk of ovarian cancer, but it is not clear whether this association applies to different histopathological types and to borderline tumors. Moreover, the temporal relations are poorly understood, and the possible role of age at first birth remains unequivocal. We have investigated these issues in a case-control study nested in a nationwide cohort of women born between 1925 and 1960 in Sweden. During follow-up until 1984.3486 invasive ovarian cancers (2992 epithelial, 330 stromal, 149 germcell, I5 not classifiable) and 510 tumors of borderline malignant potential were diagnosed. 5 individually age-matched controls (total I9 980) were selected for each case woman. After simultaneous adjustment for parity and age at first birth, increasing parity was associated with a pronounced consistent decrease in relative risk of all invasive cancers (odds ratio for each additional birth 0.81 [95X Cl 0.77-0.85]), epithelial cancer (0.81 [0.77-0.86]), stromal cancer (0.84 [0.72-0.981). and germ-cell cancer (0.71 [0.48-1.051) but a less consistent decrease for borderline tumors (0.92 [0.81-1.041). The risk of ovarian cancer decreased by about 10% for each 5-year increment in age at first childbirth (odds ratios 0.89 [0.84-0.94) epithelial
II4
Citations from the literature/International Journal of Gynecology & Obstetrics SO (1995) Ill-121
cancer, 0.92 [0.77- 1.IO] stromal cancer, 0.92 [0.65-l .32] germcell cancer, 0.93 [O.SO-I.091borderline tumors). Because our findings cannot be readily explained by theories invoking incessant ovulation or high serum concentrations of gonadotropins, new etiological hypotheses are needed. Pregnancy-dependent clearance from the ovaries of cells that have undergone malignant transformation could explain the reproductive risk factors for ovarian cancer. Lipid-soluble aotioxidaob: &carotene and cY-tocopherollevels in breast and gynecologic cancers Palan P.R.; Goldberg G.L.; Basu J.; Runowicz C.D.; Romney S.L. USA GYNECOL. ONCOL. 1994 55/l (72-77) Free radical-induced damage is etiologically implicated in many chronic diseasesincluding cancer. Epidemiologic data suggest an association between increased dietary intake of nutrients that are high in antioxidant vitamins and protection against the incidence of some human cancers. The purpose of this study was (a) to determine whether specific tissue antioxidants (&carotene and o-tocopherol) and any differences in their levels were measurablein randomly selectedhuman breast and gynecologic malignant neoplasmsand nonneoplastic tissue samples obtained from the same patient and (b) to establish normal ranges of these two antioxidant levels in human female reproductive tract tissues. Tissue samples were excised immediately from surgical specimens and released by staff pathologists from a spectrum of human female cancers. Neoplastic and adjacent nonneoplastic tissuessampleswere obtained from the same patient. Normal reproductive tract tissue sampleswere obtained from women undergoing hysterectomy for benign gynecologic conditions. Breast carcinoma and adjacent nonmalignant tissuespecimenswere obtained from women undergoing mastectomy. The concentrations of @-caroteneand o-tocopherol were measured by high-pressure liquid chromatography. In the same patient, @-carotene levels were significantly lower in the cervical (P < 0.01) and endometrial (P c 0.005)carcinoma tissuesthan the levels detectable in adjacent nonneoplastic sites. In contrast,-carotene levels were higher in the ovarian (P < 0.05), breast (P < 0.005),and vulva (P < 0.05) carcinoma tissues.The &tocopherol concentrations were significantly higher in the cancer tissues of cervix (P < 0.01) and endometrium (P < 0.001) than those in adjacent noninvolved tissue sites. The tissue concentrations of (Ytocopherol in malignant and adjacent normal sites in breast, ovary, and vulva were comparable. For the first time, the rangesfor &carotene and a-tocopherol levels in the normal female reproductive tract tissueswere also established. The present findings of contrasting tissue levels of the antioxidants (b-carotene and a-tocopherol) in breast, cervix, endometrium, ovary, and vulva cancers and in nonneoplastic tissues of the samepatient suggestan organ-specific and heterogenousdistribution. Theseantioxidants appear to be essential nutritional requirements of the human female reproductive tract and breast and are implicated in the pathophysiology and carcinogenesis of these human organs. The findings require further study of
the role of theseantioxidant nutrients in epithelial cell proliferation, maturation, and differentiation. Continuous tamoxifen treatment in asymptomatic, postmen* pausal breast cancer patients does not cause aggravation of eadometrirl pathologies Cohen I.; Tepper R.; Rosen D.J.D.; Shapira J.; Cordoba M.; Dror Y.; Altaras M.; Beyth Y. ISR GYNECOL. ONCOL. 1994 55/l (138-143) Adjuvant tamoxifen therapy for breast cancer patients has beenfound to be associatedwith various endometrial pathologic conditions, including endometrial cancer. This preliminary case control study evaluated whether prolonged and continuous exposure to tamoxifen in the menopausemay aggravate existing endometrial pathologies. Two vaginal ultrasound evaluations of endometrial thickness and histologic findings of two endometrial biopsies, performed I8 months apart, were evaluated for 25 asymptomatic, postmenopausal breast cancer patients who were continuously treated with tamoxifen. In the first endometrial biopsy, 4 patients (16.0%)were found to have endometrial pathologies: 2 patients had proliferative endometrium, 1 had hyperplastic endometrium, and I had an endometrial polyp. In the secondendometrial biopsy, none of these patients showed any endometrial pathologies. Another patient (4.0%) with no endometrial pathology in the lirst visit had endometrial hyperplasia in the secondvisit. None of the patients developed endometrial cancer, and generally there was no increasein ultrasonographically-measured endometrial widths. The results of this preliminary study may suggestthat there is no increased risk of development of endometrial pathologies during an additional I8 months of continuous tamoxifen therapy nor is there aggravation of already existing endometrial pathologies.
PREGNANCY
AND DELIVERY
Reductionof maternal-infant transmissionof humanimmunodeficiency virus type 1 with zidovudiae treatment Connor E.M.; Sperling R.S.; Gelber R.; Kiselev P.; Scott G.; O’Sullivan M.J.; VanDyke R.; Bey M.; Shearer W.; Jacobson R.L.; Jimenez E.; O’Neill E.; Bazin B.; Delfraissy J.-F.; Culnane M.; Coombs R.; Elkins M.; Moye J.; Stratton P.; Balsley J. USA NEW ENGL. J. MED. 1994331118(1173-1180) Background and Methods. Maternal-infant transmission is the primary means by which young children become infected with human immunodeliciency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks’ gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum
Journal of Gynecology & Obstetrics 50 (1995) 111-121
linear analysis, persisted within each severity stratum of cervical intraepithelial neoplasia and was independent of associated human papillomavirus infection. In human immunodeficiency virus-positive patients log-linear analysis showed that highgrade cervical intraepithelial neoplasia, the presence of human papillomavirus infection, and the severity of human immunodeficiency virus disease were independently correlated with increased nucleolar organizer regions-associated protein counts per cell. Conclusion: The results of this study indicate that the proliferative activity of cervical intraepithelial neoplasia lesions of human immunodeficiency virus-positive patients was increased compared with matched lesions from human immunodeficiency virus-negative women. This finding suggests the possibility of an increased oncogenic progression of cervical intraepithelial neoplasia lesions in human immunodeliciency virus-positive patients. Development of endometrial cancer in women on estrogen and progestin hormone replacement therapy McGonigle K.F.; Karlan B.Y.; Barbuto D.A.; Leuchter R.S.; Lagasse L.D.; Judd H.L. USA GYNECOL. ONCOL. 1994 5511 (126-132) The presenting symptoms, hormonal regimens, treatment modalities, tumor pathology, and follow-up of 25 women developing endometrial cancer while receiving postmenopausal estrogen and progestin therapy were investigated retrospectively. Patients were interviewed and hormone therapies were confirmed through medical records. Pathology specimens were reviewed. Patients received conjugated estrogens (n = 20) or another estrogen (n = 5). For those on conjugated estrogens, the mean daily dose was 0.68 mg, monthly duration was 24.9 days, and monthly dose was 17.0 mg. Women also received medroxyprogesterone acetate (n = 23) or norethindrone acetate (n = 2). The most common regimen was sequential medroxyprogesterone acetate, at a mean daily dose of 7.5 mg, monthly duration of 9.3 days, and monthly dose of 68 mg (mean duration=5.7 years). Most tumors were low stage and grade, with few demonstrating grade 3 disease (n = 2) or greater than 50% myometrial invasion (n = 2). Twenty-three (92%) had disease limited to the uterus, while two had stage IIIA disease. All are alive and disease-free after a median follow-up of 26 months. Estrogen and progestin therapy does not prevent endometrial cancer in all patients. Women who developed this tumor on sequential therapy in general received less than the recommended guidelines for daily dosage and monthly duration of progestin. Most patients had early-stage and low-grade disease. Continued vigilance in the care of women on hormone replacement therapy is necessary even when combination therapy is prescribed. Factors contributing to the accuracy in diagnosing ovarian malignancy by color doppler ultrasound Wu C-C.; Lee C.-N.; Chen T.-M.; Lai J.-I.; Hsieh C.-Y.; Hsieh F.-J. TWN OBSTET. GYNECOL. 1994 84/4 I (605-608) Objective: To determine whether resistance index values ob-
113
tained by color Doppler ultrasound contribute to the accuracy in diagnosing ovarian malignancies. Methods: Four hundred ten patients with ovarian neoplasms referred for color Doppler ultrasound evaluation were enrolled, excluding patients examined during the luteal phase. Resistance index of the intratumor arteries was measured by color Doppler ultrasound. The corresponding clinical and histopathologic information was recorded. For statistical determinations, we used the Yates corrected chi2 analysis, Fisher exact test, Student f test. and linear regression analysis. Results: Satisfactory intra-tumor artery waveforms were obtained in 96.1% (99 of 103) of ovarian malignancies. Resistance index values varied at 0.23-0.82. Regression analysis of resistance index values on tumor size and amount of ascites demonstrated a linear association (R=0.498 and 0.362, respectively; P < 0.01 in both). If we regard a resistance index of 0.4 as a cutoff value, the overall sensitivity and specificity in detecting malignancy were 68.0 and 97.4%. respectively. Primary ovarian malignancies exhibited signilicantly more false negatives (30 of 79) than malignancies metastasized to the ovary (three of 24) (P = 0.018). Malignancies containing mainly cystic components exhibited more false negatives (20 of 41) than did tumors with primarily solid components (I3 of 62) (P < 0.01). Significantly more false negatives were encountered in malignancies with larger diameters (greater than IO cm) compared to smaller ones (27 of 63 vs. six of 40; P < O.Ol), and in malignancies accompanied by considerable ascites (greater than 1000 ml) (I 3 of 25 vs. 20 of 78; P < 0.05). Conclusions: Tumor origin, size, component nature, and amount of ascites contributed to the accuracy in diagnosing ovarian malignancies using resistance index values obtained by color Doppler ultrasound. Parity, age at fist childbirth, and risk of ovarian cancer Adami H.-O.; Hsieh C-C.; Lambe M.; Trichopoulos D.; Leon D.; Persson I.; Ekbom A.; Janson P.O. SWE LANCET 1994 344/8932 ( l250- 1254) Increasing parity is associated with a reduction in the risk of ovarian cancer, but it is not clear whether this association applies to different histopathological types and to borderline tumors. Moreover, the temporal relations are poorly understood, and the possible role of age at first birth remains unequivocal. We have investigated these issues in a case-control study nested in a nationwide cohort of women born between 1925 and 1960 in Sweden. During follow-up until 1984.3486 invasive ovarian cancers (2992 epithelial, 330 stromal, 149 germcell, I5 not classifiable) and 510 tumors of borderline malignant potential were diagnosed. 5 individually age-matched controls (total I9 980) were selected for each case woman. After simultaneous adjustment for parity and age at first birth, increasing parity was associated with a pronounced consistent decrease in relative risk of all invasive cancers (odds ratio for each additional birth 0.81 [95X Cl 0.77-0.85]), epithelial cancer (0.81 [0.77-0.86]), stromal cancer (0.84 [0.72-0.981). and germ-cell cancer (0.71 [0.48-1.051) but a less consistent decrease for borderline tumors (0.92 [0.81-1.041). The risk of ovarian cancer decreased by about 10% for each 5-year increment in age at first childbirth (odds ratios 0.89 [0.84-0.94) epithelial
II4
Citations from the literature/International Journal of Gynecology & Obstetrics SO (1995) Ill-121
cancer, 0.92 [0.77- 1.IO] stromal cancer, 0.92 [0.65-l .32] germcell cancer, 0.93 [O.SO-I.091borderline tumors). Because our findings cannot be readily explained by theories invoking incessant ovulation or high serum concentrations of gonadotropins, new etiological hypotheses are needed. Pregnancy-dependent clearance from the ovaries of cells that have undergone malignant transformation could explain the reproductive risk factors for ovarian cancer. Lipid-soluble aotioxidaob: &carotene and cY-tocopherollevels in breast and gynecologic cancers Palan P.R.; Goldberg G.L.; Basu J.; Runowicz C.D.; Romney S.L. USA GYNECOL. ONCOL. 1994 55/l (72-77) Free radical-induced damage is etiologically implicated in many chronic diseasesincluding cancer. Epidemiologic data suggest an association between increased dietary intake of nutrients that are high in antioxidant vitamins and protection against the incidence of some human cancers. The purpose of this study was (a) to determine whether specific tissue antioxidants (&carotene and o-tocopherol) and any differences in their levels were measurablein randomly selectedhuman breast and gynecologic malignant neoplasmsand nonneoplastic tissue samples obtained from the same patient and (b) to establish normal ranges of these two antioxidant levels in human female reproductive tract tissues. Tissue samples were excised immediately from surgical specimens and released by staff pathologists from a spectrum of human female cancers. Neoplastic and adjacent nonneoplastic tissuessampleswere obtained from the same patient. Normal reproductive tract tissue sampleswere obtained from women undergoing hysterectomy for benign gynecologic conditions. Breast carcinoma and adjacent nonmalignant tissuespecimenswere obtained from women undergoing mastectomy. The concentrations of @-caroteneand o-tocopherol were measured by high-pressure liquid chromatography. In the same patient, @-carotene levels were significantly lower in the cervical (P < 0.01) and endometrial (P c 0.005)carcinoma tissuesthan the levels detectable in adjacent nonneoplastic sites. In contrast,-carotene levels were higher in the ovarian (P < 0.05), breast (P < 0.005),and vulva (P < 0.05) carcinoma tissues.The &tocopherol concentrations were significantly higher in the cancer tissues of cervix (P < 0.01) and endometrium (P < 0.001) than those in adjacent noninvolved tissue sites. The tissue concentrations of (Ytocopherol in malignant and adjacent normal sites in breast, ovary, and vulva were comparable. For the first time, the rangesfor &carotene and a-tocopherol levels in the normal female reproductive tract tissueswere also established. The present findings of contrasting tissue levels of the antioxidants (b-carotene and a-tocopherol) in breast, cervix, endometrium, ovary, and vulva cancers and in nonneoplastic tissues of the samepatient suggestan organ-specific and heterogenousdistribution. Theseantioxidants appear to be essential nutritional requirements of the human female reproductive tract and breast and are implicated in the pathophysiology and carcinogenesis of these human organs. The findings require further study of
the role of theseantioxidant nutrients in epithelial cell proliferation, maturation, and differentiation. Continuous tamoxifen treatment in asymptomatic, postmen* pausal breast cancer patients does not cause aggravation of eadometrirl pathologies Cohen I.; Tepper R.; Rosen D.J.D.; Shapira J.; Cordoba M.; Dror Y.; Altaras M.; Beyth Y. ISR GYNECOL. ONCOL. 1994 55/l (138-143) Adjuvant tamoxifen therapy for breast cancer patients has beenfound to be associatedwith various endometrial pathologic conditions, including endometrial cancer. This preliminary case control study evaluated whether prolonged and continuous exposure to tamoxifen in the menopausemay aggravate existing endometrial pathologies. Two vaginal ultrasound evaluations of endometrial thickness and histologic findings of two endometrial biopsies, performed I8 months apart, were evaluated for 25 asymptomatic, postmenopausal breast cancer patients who were continuously treated with tamoxifen. In the first endometrial biopsy, 4 patients (16.0%)were found to have endometrial pathologies: 2 patients had proliferative endometrium, 1 had hyperplastic endometrium, and I had an endometrial polyp. In the secondendometrial biopsy, none of these patients showed any endometrial pathologies. Another patient (4.0%) with no endometrial pathology in the lirst visit had endometrial hyperplasia in the secondvisit. None of the patients developed endometrial cancer, and generally there was no increasein ultrasonographically-measured endometrial widths. The results of this preliminary study may suggestthat there is no increased risk of development of endometrial pathologies during an additional I8 months of continuous tamoxifen therapy nor is there aggravation of already existing endometrial pathologies.
PREGNANCY
AND DELIVERY
Reductionof maternal-infant transmissionof humanimmunodeficiency virus type 1 with zidovudiae treatment Connor E.M.; Sperling R.S.; Gelber R.; Kiselev P.; Scott G.; O’Sullivan M.J.; VanDyke R.; Bey M.; Shearer W.; Jacobson R.L.; Jimenez E.; O’Neill E.; Bazin B.; Delfraissy J.-F.; Culnane M.; Coombs R.; Elkins M.; Moye J.; Stratton P.; Balsley J. USA NEW ENGL. J. MED. 1994331118(1173-1180) Background and Methods. Maternal-infant transmission is the primary means by which young children become infected with human immunodeliciency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks’ gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum