PubMed Health⌕ Search

Biomedical subjects

J N Ingle

Publications and source records attributed to J N Ingle.

At least 37 records · Page 2Linked to original sources
PubMed1999

A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma.

BACKGROUND: Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed. METHODS: One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 microg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50% vs. 37%) and a disease free interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity. RESULTS: The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone. CONCLUSIONS: There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF-I levels.

Adult↗
PubMed1999

Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis.

One hundred fifty-one postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred forty-three eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p = 0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p = 0.38). Duration of response and progression-free survival were not found to be significantly different between DES and TAM (p = 0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5-year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p = 0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms. Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy. The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.

Aged↗
PubMed1999

Metaplastic breast cancer: prognosis and response to systemic therapy.

BACKGROUND: Metaplastic breast cancer is a rare disease with little information available to guide therapy. The goals of this study were to describe the patient characteristics, systemic therapies and clinical outcomes of all patients with primary metaplastic breast cancer treated at Mayo Clinic between 1976 and 1997. PATIENTS AND METHODS: Patients were identified through the medical index of Mayo Clinic. Clinical information was abstracted from the medical record of each patient. A literature search using MEDLINE and CANCERLIT for the years 1966-1997 was performed to identify all previously reported case series in the English language containing 10 or more patients. RESULTS: Twenty-seven patients were identified with a median age at diagnosis of 59 years (range 39-90 years). The median tumor size was 3.4 cm (range 0.5-7.0 cm). One patient had metastatic disease at presentation. Twenty-three patients had information available on nodal status, estrogen receptor (ER) and progesterone receptor (PR) status. Twenty patients (87%) were node-negative and three patients (13%) were both ER and PR positive. Disease-free survival (DFS) and overall survival (OS) were assessed for those who presented with local-regional disease. The three-year DFS was 40% (95% CI: 23%-73%) and the three-year OS was 71% (95% CI: 51%-97%). In univariate analysis, those patients 60 years of age or older at diagnosis were found to have an increased DFS (P = 0.011). Among those with prior estrogen use, both DFS (P = 0.022) and OS (P = 0.003) were decreased. Thirteen patients (50%) developed metastases with a median DFS time of 2.4 years. Ten different chemotherapy regimens were utilized for metastatic disease and one partial response was observed. There were no responses to tamoxifen in four patients with metastatic disease. Median survival after the development of metastases was eight months. CONCLUSIONS: Despite presenting more commonly as node-negative disease, DFS and OS in metaplastic breast cancer is decreased compared to typical adenocarcinomas. Systemic therapy also appears to be less effective. Patients with metaplastic breast cancer, particularly those with metastatic disease could be appropriate candidates for innovative therapeutic regimens.

Adult↗
PubMed1999

Loss of immunoreactivity for human calmodulin-like protein is an early event in breast cancer development.

Cell proliferation requires calmodulin, a protein that regulates calcium-dependent enzymes involved in signal transduction pathways in eukaryotic cells. Calmodulin-like protein (CLP) is found in certain epithelial cell types, including normal breast epithelium, and, although it closely resembles calmodulin in amino acid sequence, CLP interacts with different proteins than does calmodulin. The observation that CLP mRNA expression is dramatically reduced in transformed breast epithelial cells led to two hypotheses: (1) CLP helps to maintain the differentiated state in epithelial cells; and (2) downregulation of CLP accompanies malignant transformation of breast epithelial cells. The objective of this study was to determine if the expression of CLP in human breast cancer specimens is reduced in comparison to its expression in normal breast tissue. Eighty human breast cancer biopsy specimens were analyzed immunohistochemically for CLP expression by using a polyclonal rabbit antihuman CLP antibody. CLP expression was reduced in 79% to 88% of the invasive ductal carcinoma and lobular carcinoma specimens and in a similar fraction of the ductal carcinoma in-situ specimens, compared with normal breast specimens. None of the breast cancer specimens showed an increase in CLP expression. These findings support the hypotheses that CLP behaves as a functional tumor suppressor protein and is downregulated early in breast cancer progression.

Animals↗
PubMed1999

Phase I evaluation of preirradiation chemotherapy with carmustine and cisplatin and accelerated radiation therapy in patients with high-grade gliomas.

OBJECTIVE: A Phase I study was conducted to determine the safety, toxicity, and maximum tolerated dose of preirradiation chemotherapy using carmustine (BCNU) and cisplatin in the treatment of high-grade gliomas. METHODS: Patients with newly diagnosed high-grade gliomas received BCNU and cisplatin after surgery, both before and during definitive radiation therapy. Preirradiation chemotherapy consisted of an administration of 40 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 and repeated at 8 weeks to coincide with the start of radiation therapy. Postradiation chemotherapy consisted of an administration of 200 mg/m2 BCNU once every 8 weeks for four cycles. Radiation therapy consisted of 160-cGy fractions administered twice daily for 15 days, yielding a total dose of 4800 cGy. Dose escalation of BCNU was planned. If hematological toxicity was mild, the dose of cisplatin was to be held constant and BCNU dose escalated to 50 mg/m2 on Days 1 through 3. RESULTS: Eighteen patients were studied. The hematological toxicity was dose-limiting. Grade 3 or 4 leukopenia occurred in each of 10 patients (56%), and Grade 3 or 4 thrombocytopenia occurred in each of 9 patients (50%). Other toxicities included anorexia (94%), nausea (83%), emesis (33%), alopecia (94%), mild ototoxicity (50%), and, in one patient, death as a result of BCNU pulmonary toxicity. The median survival time was 14 months. Objective responses occurred in 45% of the patients evaluable for response. The maximum tolerated dose of this combination was 50 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 before radiation and repeated in 8 weeks to coincide with the start of radiation. CONCLUSION: This schedule of the preirradiation administration of BCNU and cisplatin with accelerated hyper-fractionated radiation therapy for the treatment of high-grade gliomas provides a less toxic alternative to that of previous studies of preirradiation chemotherapy with these agents and merits further investigation.

Adult↗
PubMed1999

Combination hormonal therapy involving aromatase inhibitors in the management of women with breast cancer.

Numerous comparative clinical trials have been conducted evaluating combination hormonal therapy involving the aromatase inhibitor aminoglutethimide, but there is no evidence for any superiority of this approach over single-agent therapy alone. The advent of new aromatase inhibitors with greater potency, selectivity, and better tolerability has prompted a reconsideration of the combined therapy approach, with attention being focused on pharmacologic and endocrinologic clinical research. The value of combining newer aromatase inhibitors with other hormonal agents remains to be established.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer.

The goals of this clinical trial involving postmenopausal women with metastatic breast cancer were to: (a) examine the effects of letrozole on tamoxifen (TAM) pharmacokinetics; (b) examine estrogen suppression in patients receiving TAM plus letrozole; and (c) evaluate tolerability, toxicity, objective response, and time to progression for the combination. Postmenopausal women with measurable or evaluable metastatic breast cancer received TAM (20 mg daily) for 6 weeks, and then letrozole (2.5 mg daily) was added. To examine for any effect of letrozole on the levels of TAM and two metabolites [N-desmethyl-TAM and 4-hydroxy-TAM], serum samples were obtained at 6, 12, 18, and 24 weeks. To examine for aromatase inhibition, serum samples were obtained before treatment and at 6, 12, 18, and 24 weeks for estradiol, estrone (E1) E1 sulfate, and sex hormone-binding globulin. A total of 34 patients were entered on this trial, and 23 patients were still on study at week 24, 18 of whom had blood samples available at both week 6 and week 24. The 95% confidence interval for the mean difference between levels at week 24 and levels at week 6 was -34 to 15 ng/ml for TAM, -35 to 45 ng/ml for N-desmethyl-TAM, and -1 to 2 for 4-hydroxy-TAM. For estradiol, a significant decrease (median, 88.5%; range, 73.7-95.2%) was identified after 6 weeks of letrozole, which was maintained for an additional 12 weeks. Similar significant reductions were identified for E1. E1 sulfate levels increased after 6 weeks of TAM alone but then decreased significantly after the addition of letrozole. Sex hormone-binding globulin levels were significantly elevated after 6 weeks of TAM alone and remained elevated after the addition of letrozole. Six of the 34 patients (17.6%) achieved an objective response (95% confidence interval, 6.8-34.5%), with a median time to disease progression of 7.6 months. There was no indication of a systematic decrease in TAM, N-desmethyl-TAM, or 4-hydroxy-TAM after the additional of letrozole. Estrogen suppression induced by letrozole was substantial despite the concomitant administration of TAM. The antitumor effect of TAM plus letrozole was less than expected.

Adult↗
PubMed1998

Molecular markers in male breast carcinoma.

BACKGROUND: In contrast to female breast carcinoma, information regarding the prevalence and prognostic information of new molecular markers is limited in male breast carcinoma. The objective of this study was to assess the degree of expression and prognostic value of estrogen receptors (ER), progesterone receptors (PR), androgen receptors (AR), bcl-2, p53, HER-2/neu, cyclin D1, and MIB-1 in a cohort of male breast carcinoma patients. METHODS: A computerized search of the medical index, tumor registry, and tissue registry was used to identify 111 male patients with a diagnosis of primary adenocarcinoma of the breast seen between 1950-1992 at the Mayo Clinic. Of these, 77 patients had adequate tissue specimens available for the immunohistochemical analysis of the markers. Immunoperoxidase staining was performed by an automated avidin-biotin complex method. Progression free (PFS) and overall (OS) survival distributions were estimated using the Kaplan-Meier method. The log rank test was used to determine whether any patient characteristic, tumor feature, or molecular marker was associated significantly with PFS or OS. RESULTS: The majority of tumor specimens were positive for ER (91%), PR (96%), AR (95%), and bcl-2 (94%). Fewer positive specimens were found for cyclin D1 (58%), MIB-1 (38%), HER-2/neu (29%), and p53 (21%). The 5-year PFS and 10-year OS for the entire patient cohort was estimated to be 66% (95% confidence interval [CI], 57-77%) and 38% (95% CI, 29-50%), respectively. PFS was decreased significantly for those patients with tumors staining positively for MIB-1 (P=0.012) or negatively for cyclin D1 (P=0.009). OS was not found to differ significantly with respect to these markers. CONCLUSIONS: The nearly universal expression of hormone receptors in these tumors suggests a central role for endogenous hormones in male breast carcinoma. The high degree of AR expression would suggest that antiandrogen therapy should be explored further. The high frequency of bcl-2 positivity may implicate antiapoptotic mechanisms in the carcinogenesis of male breast carcinoma. The finding of decreased PFS in MIB-1 positive tumors supports the role of proliferative activity as a negative prognostic factor in male breast carcinoma. Positive cyclin D1 expression is associated with increased PFS in male breast carcinoma patients, which suggests that interactions among cell cycle regulatory proteins may be important in this disease.

Adult↗
PubMed1998

Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity.

The centrosome plays an important role in maintenance of cell polarity and in progression through the cell cycle by determining the number, polarity, and organization of interphase and mitotic microtubules. By examining a set of 35 high grade human breast tumors, we show that centrosomes of adenocarcinoma cells generally display abnormal structure, aberrant protein phosphorylation, and increased microtubule nucleating capacity in comparison to centrosomes of normal breast epithelial and stromal tissues. These structural and functional centrosome defects have important implications for understanding the mechanisms by which genomic instability and loss of cell polarity develop in solid tumors.

Adenocarcinoma↗
PubMed1998

Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study.

PURPOSE: To compare failure-free survival (FFS) and overall survival (OS) for patients with metastatic breast cancer treated with the gonadotropin-releasing hormone (GN-RH) agonist, goserelin versus surgical ovariectomy. PATIENTS AND METHODS: Between August 1, 1987 and July 15, 1995 138 (136 eligible) premenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive metastatic breast cancer were entered by the Southwest Oncology Group (SWOG), North Central Cancer Treatment Group (NCCTG), and Eastern Cooperative Oncology Group (ECOG). Prior chemotherapy or hormone therapy for metastatic disease was not allowed. Patients were randomly assigned to goserelin (3.6 mg subcutaneously every 4 weeks; (n = 69) versus surgical ovariectomy (n = 67). The study was initially designed as an equivalence trial with 80% power to rule out a 50% improvement in survival due to ovariectomy. However, accrual was slow and the study was terminated early, which resulted in a final power of 60% for the alternative hypothesis of equal survival distributions. RESULTS: FFS and OS were similar for goserelin and ovariectomy. The goserelin/ovariectomy death hazards ratio was .80 and the associated 95% confidence interval (CI) was .53 to 1.20. The test of 50% improvement in survival due to ovariectomy was rejected at P = .006. Goserelin lowered serum estradiol to postmenopausal levels. Hot flashes (75% v 46%) and tumor flare (16% v 3%) were more common with goserelin. CONCLUSION: Goserelin and ovariectomy resulted in similar FFS and OS. We can rule out a moderate advantage for ovariectomy. Goserelin was safe and well tolerated.

Adult↗
PubMed1997

A randomized phase II trial of two dosage levels of letrozole as third-line hormonal therapy for women with metastatic breast carcinoma.

BACKGROUND: It is common practice to utilize a series of different hormonal agents in the treatment of postmenopausal women who, despite disease progression, continue to be candidates for hormonal therapy on a clinical basis. Letrozole is a new highly selective and potent aromatase inhibitor. There are limited data on third-line hormonal therapy in general, and this study was undertaken to evaluate letrozole in this context. METHODS: A randomized trial involving two independent Phase II trials of two letrozole dosage levels, 0.5 mg and 2.5 mg per day, was performed. Eligibility requirements included failure on two prior hormonal therapies and measurable or evaluable disease. RESULTS: Ninety-one patients, 46 receiving 0.5 mg and 45 receiving 2.5 mg of letrozole per day, were assessable for response. At the lower dose, 9 patients (20%) achieved an objective response; 6 patients (13%) had this documented on 2 occasions separated by 3 months. At the higher dose, 10 patients (22%) achieved a response; 8 patients (18%) had this documented on 2 occasions separated by 3 months. The median times to progression were 97 days for the lower dose and 154 days for the higher dose. Toxicity was considered acceptable. CONCLUSIONS: Letrozole has definite antitumor activity as third-line hormonal therapy for women with metastatic breast carcinoma at doses of 0.5 and 2.5 mg per day. It is an effective and generally well-tolerated hormonal agent.

Antineoplastic Agents, Hormonal↗
PubMed1997

Mitoxantrone dose augmentation utilizing filgrastim support in combination with fixed-dose 5-fluorouracil and leucovorin in women with metastatic breast cancer.

Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2; III, 24 mg/m2; IV, 32 mg/m2; and LV, 300 mg, followed by FU, 350 mg/m2, on days 1-3. Filgrastim was given at 5 micrograms/kg/day subcutaneously on days 4-13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as the dose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts: IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts < or = 20,000/microL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%) achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.

Adult↗
PubMed1997

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer.

We performed a meta-analysis of randomized trials comparing tamoxifen to ovarian ablation carried out either by surgery or irradiation as first-line hormonal therapy for pre-menopausal women with metastatic breast cancer. Patients in all trials included were required to have measurable disease and to be currently menstruating or within 1 year of cessation of menses, and to have estrogen receptor (ER) positive or unknown disease (ER negative women were admitted to one of the studies). Individual patient data were obtained from the four studies identified and the results updated to June 1992. A total of 220 eligible patients were enrolled in the four trials. There was no difference in overall response rate between tamoxifen and oophorectomy across the four trials (p = 0.94, Mantel-Haenszel test). The odds reduction for progression was 14% +/- 12% and for mortality 6% +/- 13% in favour of tamoxifen, results which were not statistically significant (p = 0.32 and 0.72, respectively). Although the design of all four studies included a cross-over to the other therapy, only 54/111 patients receiving ovarian ablation and 34/109 patients receiving tamoxifen as primary therapy actually crossed over to the other arm at the time of disease progression. Response to initial treatment with tamoxifen was predictive of subsequent response to ovarian ablation (p < 0.05), and response to initial therapy with ovarian ablation was predictive of subsequent response to tamoxifen (p < 0.05). Support curves based on log-likelihood ratios revealed that this meta-analysis provides moderate evidence rejecting a 14% advantage for ovarian ablation compared to tamoxifen in terms of odds of disease progression. A 25% advantage for ovarian ablation with respect to odds of death is also rejected with moderate evidence. We conclude that the efficacy of tamoxifen appears to be similar to that of ovarian ablation by surgery or irradiation as first-line therapy for premenopausal, ER positive metastatic breast cancer, and is unlikely to be substantially inferior.

Adult↗
PubMed1997

Evaluation of intravenous 6-thioguanine as first-line chemotherapy in women with metastatic breast cancer.

6-Thioguanine (6-TG) is a purine analog that has marked variability in plasma concentration after oral administration. Following the development of a multiple-day i.v. regimen, we performed a phase II trial of this agent as first-line chemotherapy in women with metastatic breast cancer. Forty-one patients with measurable (31 patients) or evaluable (10 patients) disease were entered into this trial. 6-TG was administered i.v. over a 10 min period daily for 5 consecutive days, with a planned cycle length of 35 days. The daily dosage level was 55 mg/m2 in the first 15 patients, but this was increased to 65 mg/m2 in the remaining patients due to inadequate myelosuppression at the lower dose. Six patients, all with measurable disease, achieved a complete response (CR) (two patients) or a partial response (PR) (four patients). Three responses occurred at the 55 mg/m2 level and three at the 65 mg/m2 level. The 95% confidence interval (CI) for the true response rate among patients with measurable disease was 6-39%. The median time to progression was 140 days and median survival time was 460 days. The regimen was well tolerated. We conclude that 6-TG, as given in this study, has limited activity as first-line chemotherapy for women with metastatic breast cancer.

Adult↗
PubMed1997

Accelerated hyperfractionation radiation therapy after lumpectomy and axillary lymph node dissection in patients with stage I or II breast cancer: pilot study.

PURPOSE: To prospectively assess tolerance to accelerated hyperfractionation radiation therapy in patients undergoing breast-conservation therapy and to exclude, with 90% confidence, a 20% or greater risk of an acute toxic reaction of at least grade 3 (severe). MATERIALS AND METHODS: Thirty-seven patients (aged 33-80 years) with evaluatable cases received 48 Gy in twice-daily 1.6-Gy fractions to the breast and regional lymph nodes (if three or more lymph nodes were involved) and a boost of 9.6 Gy in twice-daily 1.6-Gy fractions. Acute and late effects were scored by using the Radiation Therapy Oncology Group and European Organization for the Research and Treatment of Cancer radiation morbidity criteria. RESULTS: One patient developed a grade 3 acute skin toxic reaction and another grade 3 (continuous) acute edema. There have been no grade 4 (life-threatening) acute toxic reactions, local recurrences, or cancer- or treatment-related deaths. CONCLUSION: This breast-conservation accelerated hyperfractionation radiation therapy schedule is tolerable. Additional follow-up is necessary to determine long-term morbidity and cosmesis, and further study in a larger patient group is necessary to confirm efficacy.

Adult↗
PubMed1997

Breast cancer survival and the timing of tumor removal during the menstrual cycle.

In a retrospective cohort study of 262 premenopausal breast cancer patients treated at the Mayo Clinic between 1965 and 1985, we investigated whether survival was associated with the timing of tumor removal during the menstrual cycle. Participants were women < or = 50 years old who had not used exogenous hormones, been pregnant, been lactating, or given birth within 6 months of diagnosis. The menstrual cycle day at surgery was used to assign women to group 1 (cycle days 0-7), group 2 (cycle days 8-15), or group 3 (after cycle day 15). Cox proportional hazards analysis adjusting for age at diagnosis, stage, tumor size, grade, and node involvement showed a nonsignificantly worse survival for group 2 than for group 3 [hazard ratio (HR), 1.41; 95% confidence interval (CI), 0.89-2.23]. Stratification revealed that the association between survival and timing of tumor removal during the menstrual cycle was slightly stronger among patients with stage II disease (adjusted HR, 1.56; 95% CI, 0.92-2.63). The association was the same among patients with stage II disease and node involvement (adjusted HR, 1.57; 95% CI, 0.82-3.03). Prospective studies using hormone measurements to define menstrual cycle status more accurately than the reported day of the menstrual cycle could provide further insight about the postulated association.

Adult↗