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PubMed2003

Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa).

BACKGROUND: Cervical cancer is caused by specific types of the human papilloma virus (HPV), but not all infected women develop cancer. It has been hypothesized that hormonal contraceptives may potentiate the oncogenicity of HPV infection. METHODS: In a case-control study of colored and black women in the Western Cape Province, South Africa, 524 incident cases of clinically evident invasive cervical cancer (stages 1b-1V) were compared with 1541 controls, and with a subgroup of 254 HPV-positive controls. FINDINGS: For injectable progestogen contraceptives (95% of which were depot medroxyprogesterone acetate) the overall relative risk, adjusted for confounding, was 1.0 (95% confidence interval 0.8-1.3); for combined estrogen/progestogen oral contraceptives the corresponding estimate was 0.8 (0.7-1.1). When the data were divided into categories of duration of use extending to > or = 15 years, or according to age, ethnic group, or recency of use, there was no consistent evidence of an increased risk. The findings were unchanged when the cases were compared with the HPV-positive controls. INTERPRETATION: The present findings suggest that neither injectable progestogen-only nor combined estrogen/ progestogen oral contraceptives increase the risk of clinically evident invasive cancer of the cervix.

Adult↗
PubMed2005

Cost-effectiveness of alendronate in the prevention of osteoporotic fractures in Danish women.

Pharmacological interventions for osteoporosis may reduce morbidity and mortality, but they incur additional health care costs. The aim was to quantify the additional costs and health benefits of prescribing alendronate 10 mg and calcium/vitamin D daily for 71-year-old women with a fracture risk twice that of the population average in stead of calcium/vitamin D alone. A state transition model based primarily on Scandinavian data was developed. Women were followed from age of 71 years until 100. Alendronate was assumed to reduce the fracture risk by 50%. Health benefits from the interventions were expressed in terms of life years, quality adjusted life years, and fractures avoided. Societal costs were estimated using literature estimates and Danish tariffs. All costs were measured in 2002 Danish Kroner (DKK). Future costs and benefits were discounted at 5% per year. The incremental cost per QALY gained was DKK125,000 while the cost per life year gained was DKK 374,000. The use of alendronate was cost-saving when 1) the treatment was extended to five years, 2) the risk of fracture was four times the population average, 3) the effect of alendronate was assumed to persist for three years after discontinuation of treatment, 4) a greater proportion had severe sequelae after a hip fracture, or 5) the start of therapy was delayed until age of 77 years. In conclusion, the use of alendronate compares well with other well established therapies in terms of cost-effectiveness in older women with high risk of fracture.

Aged↗
PubMedDate not supplied

[Congenital anomalies of the uterus. (Pregnancy, delivery, and the newborn].

A total of 123 women with congenital anomalies of the uterus were analysed. It has been found that earlier pregnancies terminated with abortus in a high percentage (68.09%). In the course of the last pregnancy and the first in primiparas, 39.02% of women developed one or more complications. The delivery itself was completed by cesarean section in 75.6% of parturients. In the course of labour, complications appeared in 44.71% of women; most frequently there was a premature rupture of the bag of waters and the adhered placenta. The abnormal position of the fetus was found in 54.47%, it was mostly the pelvic presentation. A comparison between the perinatal mortality in earlier deliveries and the last one has shown that there is a significant association between the use of cesarean section and perinatal mortality. In earlier deliveries the perinatal mortality rate was 48.78% and in the last pregnancy 8%. There were 19.2% before-term babies. By Apgar score 1--8, 55.73% of newborns were assessed. The babies were often hypotrophic in relation to their gestation age. A high percentage of congenital anomalies in newborns (16.8%), mostly joint deformations, was established. It is concluded that uterine congenital anomalies exert an unfavourable effect on pregnancy. They put both mother and child at risk. The risk could be diminished by a timely detection of uterine anomalies, by the appropriate therapy, and by the use of cesarean section.

Adult↗
PubMed2003

Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia.

BACKGROUND: Maternal endothelial dysfunction is a feature of established pre-eclampsia but whether this is a cause or consequence of the disorder is not clear. We tested the hypothesis that endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine (ADMA), the endogenous inhibitor of endothelial nitric oxide synthase, precede and contribute to the development of pre-eclampsia. METHODS: We assessed uterine artery doppler waveforms in 86 women at 23-25 weeks' gestation. We tested endothelial function in all women using flow-mediated dilation of the brachial artery at 23-25 weeks' gestation. Plasma concentrations of ADMA were also measured. FINDINGS: 43 women had normal uterine artery doppler waveforms and subsequently had a normal outcome. The second group of 43 had evidence of impaired placental perfusion and of these, 19 (44%) had normal outcome, 14 (33%) developed intrauterine growth restriction of the fetus (IUGR), and pre-eclampsia arose in ten (23%). Women who developed pre-eclampsia had significantly lower flow-mediated dilation than did women who had normal outcome (3.58% [SD 2.76] vs 8.59% [2.76]; p<0.0001). Irrespective of pregnancy outcome, women with evidence of impaired placental perfusion had significantly higher levels of ADMA than did women with normal doppler waveforms (2.4 micromol/L [IQR 1.97-3.14] vs 0.81 micromol/L [0.49-1.08]; p<0.0001). There was a strong inverse correlation between ADMA and flow-mediated dilation but only in the group of women who eventually developed pre-eclampsia (r=-0.8, p=0.005). INTERPRETATION: Maternal endothelial function is impaired in women who eventually develop pre-eclampsia and it occurs before the development of the clinical syndrome. Furthermore, women with high resistance placental circulation at risk of pre-eclampsia, IUGR, or both have raised concentrations of ADMA, which is a potential contributory factor for pre-eclampsia, and is associated with endothelial dysfunction in some women.

Arginine↗
PubMed1997

Incidence of non-melanocytic skin cancer in Geraldton, Western Australia.

To measure the rate at which non-melanocytic skin cancers develop, we conducted a population-based, longitudinal study in Geraldton, Western Australia. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age and registered on the electoral roll in 1987. In 1987 and again in 1992, dermatologists examined participants for skin cancers. They examined all skin areas, apart from those covered by underwear or hair. Subjects were asked about skin cancers that they had had treated between the 2 surveys. When all skin cancers were counted, the incidence rates of basal cell carcinoma were 3,379 per 100,000 person-years in women and 7,067 per 100,000 in men; those of squamous cell carcinoma were 501 per 100,000 in women and 775 per 100,000 in men. Sixteen percent of men and 14% of women developed at least one basal cell carcinoma; 2.8% of men and 2.2% of women had at least one squamous cell carcinoma. Most incident skin cancers were diagnosed at the second examination. More than half of the subjects who had a skin cancer at the first examination developed another. Squamous cell carcinomas occurred almost exclusively on parts of the body that are usually exposed. Basal cell carcinomas were common on the head, neck and trunk but not on the forearms and backs of hands. A quarter of people with a skin cancer on an exposed site also had one on the trunk. Our results show that skin cancer is extremely common in this population and frequently undiagnosed. Multiple skin cancers occur commonly, and skin cancers on exposed sites often are associated with skin cancers on less exposed sites.

Adult↗
PubMed2003

A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden).

OBJECTIVES: Reports suggest that combined estrogen plus progestin hormone replacement therapy (HRT) confers a higher breast cancer risk than estrogen alone. We aimed to establish whether breast cancer risk depends on the type of HRT formula. METHODS: The cohort consisted of 6586 women, aged 50-64 years, from the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained information such as HRT use through a questionnaire between December 1995 and February 2000. New breast cancers were identified through the South Swedish tumor registry. RESULTS: Between inclusion and December 2001, 101 women developed breast cancer. Only ever use of the continuous combined estrogen plus progestin (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p = 0.000001). Compared with never users, exclusive CCEP users had the highest age-adjusted hazard ratio HR 3.3 (95% CI: 1.9-5.6; p < 0.001), followed by users of CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4-5.5; p = 0.003). No significant increase was seen in women who exclusively used other HRT formulas. CONCLUSION: Women who used CCEP had over three times the risk of developing breast cancer compared with never users and twice the risk compared with users of other types of HRT.

Breast Neoplasms↗
PubMed1995

Hypertensive and normal pregnancy: a longitudinal study of blood pressure, distensibility of dorsal hand veins and the ratio of the stable metabolites of thromboxane A2 and prostacyclin in plasma.

OBJECTIVE: By combining serial measurements of the circulating concentrations of thromboxane A2 and prostacyclin with measurements of venous distensibility (taken during the pregnancies of both normal women and those with pregnancy induced hypertension or pre-eclampsia), to test the following hypotheses: 1. that changes in the venous plasma ratio of thromboxane (TXB2) and 6-keto-PGF1 alpha would correlate with changes in the blood pressure of women developing and recovering from pregnancy induced hypertension or pre-eclampsia and 2. that changes in venous distensibility would correlate with changes in arterial blood pressure in pregnancy induced hypertension or pre-eclampsia. DESIGN: Prospective, longitudinal cohort study. SETTING: John Hunter Hospital clinic, Newcastle, Australia. SUBJECTS: One hundred and sixty primiparous women, recruited when presenting for their first routine antenatal visit, were investigated at, or close to, 19, 28 and 37 weeks of gestation; a subgroup was also studied in the postnatal period. The measurements of the patients who developed pregnancy induced hypertension or pre-eclampsia were compared with those of controls selected from the cohort. MAIN OUTCOME MEASURES: Serial measurements of the circulating concentrations of the stable metabolites of thromboxane A2 and prostacyclin (TXB2 and 6-keto-PGF1 alpha, respectively), venous distensibility and immediate (no rest) and resting (for at least 30 min) blood pressures. RESULTS: There was no significant difference between the subject and control groups at any time during or after the pregnancy in the concentrations of prostaglandin metabolites, their ratio or venous distensibility. In contrast, there was a significant difference between the groups at 19 weeks for immediate and resting readings of diastolic pressure (6 mmHg (95% CI 1.5 to 10.5) and 4 mmHg (95% CI 0.1 to 7.9), respectively). These differences increased through the pregnancy but mean postnatal readings for the groups were almost identical suggesting that the subjects were not intrinsically hypertensive compared with controls. Blood pressures for the subject group, both immediate and resting, were significantly different from the 19 week readings at 28 weeks (diastolic) and at 37 weeks (systolic and diastolic). The only significant change from first readings among controls was in postnatal systolic pressure which was significantly higher than 19 week values, probably reflecting the vasodilatation, with accompanying hypotension, of early, normal pregnancy. This difference was not observed in those who subsequently developed pregnancy induced hypertension or pre-eclampsia. CONCLUSIONS: Our study was unable to demonstrate differences in circulating metabolites or venous distensibility between normotensive women and those with pregnancy induced hypertension or pre-eclampsia. If pregnancy induced hypertension or pre-eclampsia in humans represents not so much the presence of abnormal constrictor influences as a process initiated by failure of normal vasodilatation in early pregnancy, studies carried out later may detect mainly adaptive and secondary changes.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Hormonally induced differentiation: a novel approach to breast cancer prevention.

Breast cancer, one of the most common neoplasms in women, develops more frequently in those who are nulliparous or late parous, who experience early menarche and late menopause and have a family history of breast cancer. Early parity, late menarche, early menopause, and hormone deprivation exert a protective effect. The mechanisms modulating these variations in malignancy susceptibility are not known. Epidemiologic and experimental studies indicate that malignancies develop in the mammary gland as a result of exposure to carcinogenic stimuli (i.e., chemical carcinogens, radiation). Neoplastic transformation requires that the gland be under specific developmental and age-related conditions at the time of exposure to such agents. In the rat, maximal susceptibility to neoplastic transformation is exhibited by the highly proliferating and undifferentiated gland of the young, virgin, intact females, whereas the fully differentiated gland of parous rats and virgin rats treated with the placental hormone human chorionic gonadotropin is protected from tumor development. Hormonally induced differentiation of the mammary gland is a novel approach to breast cancer prevention and therapy. The development of clinical protocols capitalizing on the protective effect of hormonal treatments mimicking pregnancy in humans is required to validate observations in experimental animal models, and to determine how they relate to epidemiologic and clinical findings. The feasibility of this approach is supported by the observed parallelism between humans and experimental models in both the site of cancer origin and the changes in breast development occurring with parity. Breast cancer initiates in terminal ductal lobular units or lobules type 1, the most undifferentiated structures frequently found in the breast of young nulliparous women.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Angiotensin-converting enzyme and angiotensinogen gene polymorphisms are non-randomly distributed in oral contraceptive-induced hypertension.

OBJECTIVES AND METHODS: Oral contraceptives (OC) usage increases serum angiotensinogen levels to three to five times normal and about 5% of these women develop arterial hypertension. The genetic contribution to this susceptibility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contraceptives, for three genetic polymorphisms in genes of the renin-angiotensin system: an insertion/deletion (I/ D) in the angiotensin converting enzyme (ACE) gene, the T235M polymorphism of the angiotensinogen gene (AGT) and a point mutation in its promoter. RESULTS: After cessation of oral contraception the mean arterial pressures of the hypertensive women were separable into two non-overlapping groups; 88 of the women remained hypertensive and 61 returned to normal blood pressure. Both groups of hypertensive women had a similarly higher frequency of hypertensive relatives than the normotensive women, but were otherwise similar. The 235T allele of AGT was significantly increased in frequency in the 61 oral contraceptive-inducible hypertensive women compared with the controls and the 88 women that remained hypertensive. The ACE I/D genotypes were similarly distributed within the three groups of women, but were distinctly non-random in the oral contraceptive-induced hypertensive women when they were also classified by AGT genotype. CONCLUSION: This statistical interaction of genotype frequencies suggests that the genetic basis of susceptibility to OC-induced hypertension is complex.

Adult↗
PubMed1998

Systemic antibiotic prophylaxis in elective cesarean delivery.

OBJECTIVE: To test the value of using prophylactic antibiotics at elective cesarean delivery. METHOD: One-hundred and twenty women delivered by elective cesarean in the absence of labor and before the rupture of membranes were randomized to receive either 1.5 g of cefuroxime intravenously at cord clamping (n = 59) or no prophylaxis (control group, n = 61). RESULTS: Twelve women developed febrile morbidity (six study, six control, P = 0.09). Of these, five had endometritis (two study, three control, P = 0.09) and two had wound infection (one study, one control, P = 0.09). Ten more women had microbiological evidence of endometritis and wound infection (six study, four control, P = 0.08). There was no significant difference in the hospital stay (6.5 days study, 6.8 days control, P = 0.06). Staphylococcus aureus was the commonest pathogen accounting for 14 infection episodes. Amniotic fluid culture could not predict the development of infection. CONCLUSION: Administration of prophylactic antibiotics at elective cesarean deliveries was not associated with decreased postoperative morbidity.

Adult↗
PubMed1977

Roll-over test.

One hundred randomly selected nulliparous, normotensive women were subjected to the roll-over test between 28 and 32 weeks' gestation. Twenty-five women had a positive test. Thirteen of those 25 women developed pre-eclampsia requiring magnesium sulfate therapy. Eight had transient hypertension during labor requiring no therapy. Four had no evidence of hypertension during pregnancy. A false-positive rate for the 25 women with a positive roll-over test was 16 per cent. Seventy-five women had a negative roll-over test. Sixty-eight of those women had no evidence of hypertension of pregnancy. Seven had evidence of transient hypertension during labor requiring no therapy. A false-negative test was present in 10 per cent of the 75 patients with a negative roll-over test. In no case did a patient with a negative test develop pre-eclampsia. The roll-over test is recommended as a routine test for every pregnant patient between 28 and 32 weeks' gestation for the early diagnosis of hypertension of pregnancy.

Blood Pressure↗
PubMed2002

Is sexual intercourse a significant cause of haematuria?

OBJECTIVES: To determine whether recent sexual intercourse might be a cause of microscopic haematuria in patients referred to a urological unit following dipstick detection of urinary haemoglobin. SUBJECTS AND METHODS: Forty-eight volunteers (24 men and 24 women) consented to have heterosexual intercourse with their regular partner, and to provide samples of urine for testing before and from the first void on the morning after intercourse. After appropriate instruction, volunteers tested their own urine for the presence of blood using standard dipsticks. Any volunteer with haematuria either before or after intercourse was offered a standard haematuria assessment. The results were analysed using the chi-squared test. RESULTS: None of the volunteers tested positively for haematuria immediately before sexual intercourse; six of the 24 women (25%), but no men, became positive after intercourse (P < 0.01). Only one of the six women accepted the offer of a haematuria evaluation and no pathology was identified. CONCLUSION: These results suggest that up to a quarter of women develop microscopic haematuria as a direct result of sexual intercourse. A history of recent sexual intercourse should therefore be considered when assessing the clinical significance of microscopic haematuria in women.

Adult↗
PubMed2006

The effects of childbirth-related post-traumatic stress disorder on women and their relationships: a qualitative study.

There is converging evidence that 1%-2% of women develop post-traumatic stress disorder (PTSD) as a result of childbirth. The current study aimed to explore the long-term effects of childbirth-related PTSD on women, their relationship with their partner and their relationship with their child. Semi-structured interviews were carried out with six women who reported clinically significant PTSD after birth, ranging from 7 months to 18 years beforehand. Interviews were transcribed and analysed using thematic analysis. Childbirth-related PTSD was found to have wide-ranging effects on women and their relationships. Women reported changes in physical well-being, mood and behaviour, social interaction, and fear of childbirth. Women reported negative effects on their relationship with their partner, including sexual dysfunction, disagreements and blame for events of birth. The mother-baby bond was also seriously affected. Nearly all women reported initial feelings of rejection towards the baby but this changed over time. Long-term, women seemed to have either avoidant or anxious attachments with their child. It is concluded that childbirth-related PTSD can have severe and lasting effects on women and their relationships with their partner and children. Further research is needed to compare this to normal difficulties experienced by women after having children.

Adult↗
PubMed1996

Prospective study of relative weight and risk of breast cancer: the Breast Cancer Detection Demonstration Project follow-up study, 1979 to 1987-1989.

Despite extensive research on obesity and breast cancer in recent decades, inconsistencies in the literature exist. The authors examined prospectively the relation between adult relative weight (weight (kg)/height (m)1.5) and breast cancer risk in a cohort of 54,896 women aged 31-89 years who had previously participated in the Breast Cancer Detection Demonstration Project. During a mean follow-up period of 7 years, 226 of the premenopausal women and 1,198 of the postmenopausal women developed breast cancer. Analysis was performed using Cox proportional hazards regression methods with age as the underlying time variable and adjusted for the effects of potential confounders. Among postmenopausal women, the risk of breast cancer increased with increasing relative weight (p < 0.05 for trend); relative risk for the highest compared with the lowest quintile for relative weight was 1.3 (95% confidence interval (CI) 1.1-1.6). This association was modified by age at diagnosis, with relative risks of 1.1 (95% CI 0.8-1.4), 1.2 (95% CI 0.8-1.7), and 1.8 (95% CI 1.3-2.5), respectively, for women aged < 60, 60-64, and > or = 65 years. The higher risk of breast cancer among the older and overweight women was largely confined to women whose weights were measured during the postmenopausal but not the premenopausal period. This risk pattern was observed among the naturally menopausal women, but was also apparent in the smaller group of women with bilateral oophorectomy or hysterectomy with one ovary retained. Among premenopausal women, adult relative weight was not associated with breast cancer risk. These findings suggest that the inconsistencies in the literature on obesity and breast cancer may be due in part to the differing age distributions of the populations studied. The authors conclude that prevention of obesity throughout adulthood, particularly after menopause, may help reduce breast cancer among older women.

Adult↗
PubMed1990

Mammographic changes associated with postmenopausal hormone replacement therapy: a longitudinal study.

A retrospective study of radiologic findings from 50 postmenopausal women who underwent hormone replacement therapy was performed to determine the frequency and distribution of changes in the screen-film mammographic appearance of breast tissue between pretreatment and posttreatment mammography. Twelve (24%) of the women developed increased parenchymal density during a median follow-up of 18 months (range, 6-39 months). Mammographic changes included diffuse increase in density in seven (14%) of the women; increased multifocal, asymmetric densities in two (4%); and cyst formation in three (6%). A greater percentage of women who received estrogen-progesterone replacement (26%, 10 of 38) demonstrated changes than those who received estrogen alone (17%, two of 12), but the difference was not statistically significant. The authors conclude that benign increases in mammographic density associated with postmenopausal hormone replacement therapy are not uncommon, and they suggest that the serial changes observed in some women may diminish the sensitivity of mammography for the earlier detection of breast cancer.

Adult↗
PubMed1992

Cyclophosphamide pharmacokinetics: correlation with cardiac toxicity and tumor response.

BACKGROUND: Cyclophosphamide, which forms the nucleus for virtually all preparative regimens for autologous bone marrow transplantation (ABMT), is an alkylating agent of which cytotoxicity is not directly caused by the parent compound but by its biologically active metabolites. Its nonmyelosuppressive toxicity in the ABMT setting is cardiomyopathy. We attempted to determine any correlation between plasma levels of total cyclophosphamide and the subsequent development of cardiac dysfunction. PATIENTS AND METHODS: Analyses of plasma levels and the derivation of plasma concentration-time curves (area under the curve [AUC]) were performed in 19 women with metastatic breast carcinoma, who received a continuous 96-hour infusion of cyclophosphamide, thiotepa, and carboplatin (CTCb) with ABMT. The assay for total cyclophosphamide measures the inactive parent compound; reliable assays of the active metabolites of cyclophosphamide are not yet available. RESULTS: Six of 19 women developed moderate, but transient, congestive heart failure (CHF) as assessed by clinical and radiologic criteria. These patients had a significantly lower AUC of total cyclophosphamide (median, 2,888 mumol/L/h) than patients who did not develop CHF (median, 6,121 mumol/L/h) (P less than .002). Median duration of tumor response in these patients was also more durable; at least 22 months in patients with lower AUCs versus a median of 5.25 months in those with higher AUCs (P = .008). CONCLUSION: These pharmacokinetic data support the premise that enhancement of cyclophosphamide activation may lead to both greater tumor cytotoxicity and increased but reversible end-organ toxicity. Early analysis of pharmacokinetic data may allow modulation of cyclophosphamide administration in an attempt to enhance therapeutic efficacy.

Adult↗
PubMed1993

Eliminating the risk of life-endangering complications following overstimulation with menotropin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed. RESULTS: None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally. CONCLUSION: This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation.

Adult↗
PubMed2001

Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk.

PURPOSE: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. METHODS AND MATERIALS: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for >or= 10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. RESULTS: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer second malignancy. A positive family history increased the risk of contralateral breast cancer, but not non-breast cancer malignancies. The risk of a contralateral breast cancer increased as the number of affected relatives increased. Tamoxifen resulted in a nonsignificant decrease in contralateral breast cancer and an increase in non-breast cancer second malignancies. The 5-and 10-year cumulative incidences for leukemia and lung cancer were 0.08% and 0.2%, and 0.8% and 1%, respectively. There was no significant effect of chemotherapy or the regions treated with radiation on contralateral breast cancer or non-breast cancer second malignancy. The most common types of second non-breast cancer malignancies were skin cancers, followed by gynecologic malignancies (endometrial), and gastrointestinal malignancies (colorectal and pancreas). CONCLUSION: The 10-years cumulative incidence of a second cancer in this study was 16%. Young age and family history predicted for an increased risk of contralateral breast cancer, and older age predicted for an increased risk of non-breast cancer malignancy. The majority of patients treated with conservative surgery and radiation with or without adjuvant systemic therapy will not develop a second cancer. Long-term follow-up is important to document the risk and patterns of second cancer, and knowledge of this risk and the patterns will influence surveillance and prevention strategies.

Adult↗