Search PubMed⌕ Search

Biomedical subjects

Lynn C Hartmann

Publications and source records attributed to Lynn C Hartmann.

At least 37 records · Page 2Linked to original sources
PubMed2004

Surgical risk reduction: prophylactic salpingo-oophorectomy and prophylactic mastectomy.

Investigators have used retrospective and prospective study designs to provide much needed data on the extent of risk reduction after prophylactic oophorectomy and mastectomy in women at increased risk for breast and ovarian cancer. In this publication we identify those women who may wish to consider prophylactic surgery, review data demonstrating the efficacy of prophylactic surgery, and discuss potential surgical complications. We also present data about the frequency of use and psychosocial impact of prophylactic surgery in this typically young group of women. Finally, we provide general treatment guidelines for the practicing clinician.

Breast Neoplasms↗
PubMed2004

Bilateral oophorectomy and breast cancer risk reduction among women with a family history.

PURPOSE: We investigated whether removal of the ovaries is an appropriate risk reduction option for women at elevated risk of breast cancer based on family history of breast cancer. PATIENTS AND METHODS: This question was investigated among a group of 851 women less than age 60 who underwent bilateral oophorectomy between 1970 and 1994 for various reasons. Questionnaire information was collected from 680 (80%) and women were grouped into family risk categories. Reported occurrences of breast cancer were compared to expected rates based on the Gail model. RESULTS: The number of observed breast cancers among women in the cohort was lower than expected for all levels of familial risk, with women in the highest risk groups experiencing about half to one-fourth the number of cancers expected. The apparent protective effect of oophorectomy was stronger among women who were both premenopausal and less than age 50 at time of surgery. CONCLUSION: These data support oophorectomy as a valid breast cancer prevention option for women of all risk levels.

Adult↗
PubMed2003

Microsatellite instability in hereditary and sporadic breast cancers.

Sporadic cancers and familial breast cancers are characterized by an increase in genetic instability. Little is known about whether mismatch repair defects accompany this genetic instability. We investigated invasive and/or in situ breast cancers from 30 women with deleterious BRCA1/2 mutations and unclassified variant BRCA1/2 alterations. Forty cases of sporadic breast cancers were also investigated, including 7 medullary carcinomas. Malignant and benign lesions were examined from all cases to better understand tumor progression. Automated immunohistochemistry, with antibodies directed against hMLH1 and hMSH2, was used to screen cases for possible mismatch repair defects. When loss of expression was noted, DNA ploidy was performed by cytomorphometry. DNA, after laser microdissection, was extracted from a majority of familial cases and their corresponding controls, and microsatellite instability analysis was performed. None of the familial or sporadic cases had loss of hMSH2 expression. All but one lesion, a DCIS arising in a deleterious BRCA2 mutation carrier, had loss of hMLH1 expression and a tetraploid profile by image cytomorphometry. There was no MSI in any explored lesions (n = 34), as determined by molecular analysis, including the DCIS with loss of hMLH1 expression. We conclude that DNA mismatch repair defects involving hMLH1 and hMSH2 underexpression are extremely rare events in sporadic and familial breast cancer. Mismatch repair gene mutations may be secondary random events in breast cancer progression.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Reoperations after prophylactic mastectomy with or without implant reconstruction.

BACKGROUND: The authors characterized the unanticipated reoperations after prophylactic mastectomy, with or without implant reconstruction. METHODS: The surgical cohort was comprised of 1417 women with a family history of breast carcinoma. The women received a prophylactic mastectomy with (bilateral, n = 593; contralateral, n = 506) or without reconstruction (n = 318) at the Mayo Clinic (Rochester, MN) between 1960 and 1993. Reoperations and indications for reoperation were compiled from medical records and a patient survey. RESULTS: Three hundred eighteen women received a bilateral (n = 39) or contralateral (n = 279) prophylactic mastectomy without reconstruction. With a median follow-up of 15 years, 18 women (6%) required reoperation. Most of these reoperations occurred within the first year after prophylactic mastectomy. Five hundred ninety-three women had reconstruction with implants following bilateral prophylactic mastectomy. Approximately one-half of the women (52%) required at least 1 unanticipated reoperation during a median follow-up of 14 years. Approximately 39% of all reoperations occurred within 1 year of breast reconstruction and 69% within 5 years. Implant-related issues were the most common cause for reoperation. Some women with breast carcinoma elected to receive contralateral prophylactic mastectomy with therapeutic mastectomy for the affected breast. Five hundred six women received reconstruction with implants. During a median follow-up of 8.8 years, 189 women (37%) required unanticipated reoperation. The most common indication was implant-related issues. The time course of reoperations was similar to that for women in the bilateral group. CONCLUSIONS: Surgical reoperations were fairly common among women who received prophylactic mastectomy with implant reconstruction. Most of the reoperations were implant related. Reoperations were fairly uncommon after prophylactic mastectomy without reconstruction.

Adult↗
PubMed2003

Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer.

The levels of lysophosphatidic acid (LPA) are consistently elevated in the ascites of ovarian cancer patients, suggesting that ovarian cancer cells are exposed to an LPA replete environment. LPA stimulates cell proliferation, cell survival, resistance to cisplatin, production and activation of proteases, invasiveness and production of the neovascularizing factors, vascular endothelial growth factor, and interleukin 8. Although ovarian cancer cells can produce LPA, this may not be the major reason for altered LPA levels in ascites. We have demonstrated that the major mechanism of degradation of LPA by ovarian cancer cells is through a lipid phosphate phosphatase (LPP)-like activity. We demonstrate herein that LPP-1 mRNA is decreased in the majority of ovarian cancers. This is recapitulated in ovarian cancer cell lines, where LPP-1 RNA levels are lower than those in normal ovarian epithelium and immortalized ovarian epithelial cells. Introduction of LPP-1 into ovarian cancer cell lines results in increased LPA hydrolysis, which is associated with a marked inhibition of cell proliferation and colony-forming activity and a marked increase in apoptosis. Thus, the LPA-rich environment of the ovarian cancer cell in vivo and the subsequent effects of cellular pathophysiology may be a consequence of both increased LPA production and decreased LPA metabolism by ovarian cancer cells.

Cell Division↗
PubMed2003

Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers.

BACKGROUND: BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS: The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS: The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS: The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.

Adenocarcinoma↗
PubMed2003

Long-term follow-up of women with ovarian cancer after positive second-look laparotomy.

OBJECTIVE: Previous reports indicate that cytoreduction and salvage therapy with P32 or whole abdominal radiation may improve survival in patients with positive findings at second-look laparotomy (SLL). The aim of this investigation was to determine whether these findings held true with extended follow-up and a larger patient cohort. METHODS: From 1977 (the year platinum-based chemotherapy was introduced to our institution) to 1989, 150 patients had persistent disease at SLL. Relevant clinical information was extracted through retrospective chart review. RESULTS: One hundred forty-five patients were followed until death, with a median follow-up of 15.4 years for the 5 living patients. Median actuarial survival from the time of SLL was 18 months. Tumor grade (P = 0.003) and pre- and post-SLL tumor size (P < 0.0001) were significant determinants of survival by univariate analysis. Patients with microscopic disease or those with < or =1 cm disease rendered microscopic at SLL had improved survival relative to those with < or =1 cm and macroscopic disease following SLL (P = 0.03) (median survivals of 3.3, 2.5, and 1.4 years, respectively). In contrast, median survival of those with >1 cm disease cytoreduced to microscopic disease was no different than those with macroscopic residual, even if < or =1 cm (1.3 and 1.0 years, respectively). After adjusting for tumor size, salvage treatment was not a significant predictor of survival. CONCLUSION: With long-term follow-up there was no suggestion that the type of salvage therapy (e.g., P32 or WART) influenced survival. Rather, low-grade disease and low tumor burdens following cytoreduction were associated with improved survival on multivariate analysis.

Aged↗
PubMed2003

Her-2/neu expression in ovarian cancer: pre- and postexposure to platinum chemotherapy.

OBJECTIVE: Our objective was to determine if the level of Her-2/neu expression in advanced ovarian cancer changed after platinum-based chemotherapy. METHODS: Tissue samples from 43 patients who had surgery for ovarian cancer between 1991 and 2001 at the Mayo Clinic were stained for Her-2/neu expression using the DAKO kit and reviewed independently by two pathologists. Patient charts were reviewed for demographic data, clinical course, chemotherapy, and survival times. RESULTS: Her-2/neu expression was 0 in 30 patients (69.76%), 1+ in 12 patients (27.9%), and 3+ in 1 patient (2.32%) before chemotherapy. After platinum chemotherapy, Her-2/neu expression changed from 0 to 1+ in 7 patients, from 1+ to 0 in 4 patients, 0 to 2+ in 1 patient, and 1+ to 2+ in 2 patients and no change was seen in 29 patients. Both pathologists agreed in all instances when the score was 0 or 1+ and disagreed in two instances between a negative and a weakly positive staining. CONCLUSIONS: Our findings indicate a low level of overexpression of Her-2/neu at the time of primary diagnosis of epithelial ovarian cancer. Relapsing tumors show no significant change in the intensity of Her-2/neu expression after platinum-based chemotherapy. Further prospective studies are needed to confirm these findings and to ascertain whether platinum chemotherapy indeed has no effect on Her-2/neu expression.

Adult↗
PubMed2003

Heterogeneous role of caspase-8 in fenretinide-induced apoptosis in epithelial ovarian carcinoma cell lines.

The mechanism of action of fenretinide, a synthetic retinoid currently undergoing testing as a chemopreventive and chemotherapeutic agent, is incompletely understood. In the present study, fenretinide caused apoptotic changes, including DNA fragmentation and cleavage of caspase substrates, in six low-passage ovarian cancer cell lines. However, the caspase activation pathway used by this agent varied. Transient transfection of cDNA-encoding cytokine response modifier A (CrmA), a caspase-8 inhibitor, diminished fenretinide-induced death in OV177 cells. Likewise, IETD(OMe)-fluoromethylketone (fmk) inhibited fenretinide-induced apoptosis by >80% in OV177 or OV266 cells and by approximately 50% in OV17, OV167, or OV207 cells. Further analysis demonstrated that inhibition of Fas ligand, tumor necrosis factor-alpha, or TRAIL signaling with blocking reagents did not affect fenretinide-induced apoptosis, raising the possibility that fenretinide activates caspase-8 in a death receptor-independent manner. In contrast, CrmA transfection or IETD(OMe)-fmk treatment did not inhibit fenretinide-induced apoptosis in OV202 cells. These divergent behaviors did not correlate with increased levels of procaspase-10, which is relatively resistant to CrmA and IETD(OMe)-fmk, nor with the expression of procaspase-8 and -9, apoptotic protease activating factor-1, or cellular FLICE-like inhibitory protein. Similarly, fenretinide treatment increased ceramide levels equally in cells that do (OV177) and do not (OV202) rely on caspase-8 to initiate apoptosis. These results indicate that synthetic retinoids can use caspase-8 as an initiating caspase, but they also indicate unexpected heterogeneity in caspase activation pathways among closely related cell lines.

Apoptosis↗
PubMed2003

Risk of breast cancer and breast cancer characteristics in women treated with supradiaphragmatic radiation for Hodgkin lymphoma: Mayo Clinic experience.

OBJECTIVE: To evaluate the overall risk of breast cancer and breast cancer characteristics in women given supradiaphragmatic radiation therapy for Hodgkin lymphoma. PATIENTS AND METHODS: Medical records of 653 female patients who received supradiaphragmatic radiation therapy for Hodgkin lymphoma at the Mayo Clinic in Rochester, Minn, between 1950 and 1993 were abstracted, and follow-up questionnaires were mailed. In 4 patients, breast cancer was diagnosed before Hodgkin lymphoma was discovered. RESULTS: The median age of 649 patients at supradiaphragmatic radiation therapy was 31.8 years (range, 2.6-86.5 years). The median duration of follow-up was 8.7 years (range, < 1-47.9 years). In 30 patients, breast cancer developed (bilaterally in 4 patients) after supradiaphragmatic radiation therapy; the median interval was 19.9 years (range, 0.7-423 years). The median age at breast cancer diagnosis was 44.4 years (range, 27.5-70.8 years). The standardized morbidity ratio for breast cancer after supradiaphragmatic radiation therapy was 2.9 (95 % confidence interval [CI], 2.0-4.2) (P < .001). Breast cancer risk significantly increased 15 to 30 years after patients received supradiaphragmatic radiation therapy, and risk was inversely related to age at supradiaphragmatic radiation therapy until age 30 years. The standardized morbidity ratio for patients younger than 30 years at supradiaphragmatic radiation was 8.5 (95% CI, 53-13.1) vs 1.2 (95% CI, 0.5-2.2) for those aged 30 years or older (P < .001). Splenectomy increased breast cancer risk (P = .01). Breast cancer detection was by self-examination in 15 cancers, by mammography in 13, and by clinical examination in 4; in 2 cancers, the mode of detection was unknown. Modified radical mastectomy was used to treat breast cancer. CONCLUSION: The increased risk of breast cancer in survivors of Hodgkin lymphoma given supradiaphragmatic radiation therapy appears to be limited to patients who are younger than 30 years at radiation therapy or to those who have undergone splenectomy.

Adult↗
PubMed2002

Intraperitoneal therapy of ovarian cancer using an engineered measles virus.

The use of replicating viruses for cancer therapy (virotherapy) holds much promise. We reported previously that the live attenuated Edmonston B vaccine strain of measles virus (MV-Edm) had antineoplastic efficacy against hematological malignancies. In this study, we demonstrate that a recombinant MV-Edm, genetically engineered to express an inert soluble marker peptide (MV-hCEA), is potent against human epithelial ovarian cancer cells in vitro and in vivo. The virus was selectively oncolytic for ovarian tumor cells but caused minimal cytopathic damage on nontransformed ovarian surface epithelium and mesothelium. In contrast to nontransformed cells, the ovarian tumor cells expressed high levels of the measles virus receptor CD46. When injected directly into large established s.c. SKOV3ip.1 human epithelial ovarian xenografts in athymic mice, the virus induced complete regression of 80% of the tumors. i.p. administration of virus enhanced the median survival of mice with advanced i.p. SKOV3ip.1 tumors by >50 days. In addition, we could easily follow the kinetic profile of viral gene expression in the treated mice by determining serum levels of the virally encoded marker peptide (soluble human carcinoembryonic antigen). Trackable recombinant measles viruses warrant further investigation for therapy of ovarian cancer.

Animals↗
PubMed2002

High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases.

PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of (153)Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer. PATIENTS AND METHODS: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of (153)Sm-EDTMP. RESULTS: Thirty patients were treated with (153)Sm-EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of (153)Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after (153)Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after (153)Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 x 10(6) CD34(+)/kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status. CONCLUSION: (153)Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi (153)Sm-EDTMP/kg requires PBPC grafts with more than 2 x 10(6) CD34(+)/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.

Adolescent↗
PubMed2002

Multimodal therapy including neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for stage IIB to IV cervical cancer.

OBJECTIVE: The purpose of this study was to determine the survival rates and toxicity levels that are associated with multimodal therapy (including neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC]) in patients with stage IIB to IVB cervical cancer. STUDY DESIGN: We retrospectively reviewed the cases of 49 patients who were treated between 1989 and 1997 with neoadjuvant MVAC for advanced cervical cancer. RESULTS: The clinical response rate was 90% (27 partial responders, 17 complete responders). Grade 3 or greater toxicity was mostly limited to neutropenia; no deaths were attributed to MVAC. Combined therapy after MVAC included operation in 34 patients (69%) and radiation in 41 patients (84%). Twenty-one patients (43%) had <2 cm residual tumor at histologic evaluation. Pelvic control was achieved in 86% of patients. Five-year disease-specific survival for patients with stage III disease was 60%. CONCLUSION: For patients with advanced cervical cancer, neoadjuvant MVAC had a high response rate (90%) and an acceptable toxicity level. Compared with historic control subjects, multimodal treatment may be associated with improved rates of pelvic control.

Adult↗
PubMed2002

Long-term survival of patients with advanced/recurrent carcinoma of cervix and vagina after neoadjuvant treatment with methotrexate, vinblastine, doxorubicin, and cisplatin with or without the addition of molgramostim, and review of the literature.

A randomized phase III study was conducted to assess the addition of molgramostim (GM-CSF) to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in terms of response rate, progression-free survival, and survival in women with advanced, recurrent, or metastatic carcinoma of the cervix or vagina. Patients received four 4-week cycles of methotrexate 30 mg/m2 IV days 1, 15, 22; vinblastine 3 mg/m2 IV days 2, 15, 22; doxorubicin 30 mg/m2 IV day 2; and cisplatin 70 mg/m2 IV day 2 with or without GM-CSF 5 microg/kg every 12 hours subcutaneously days 3 to 12. They were then reevaluated for operability. Those who were not surgical candidates were offered additional chemotherapy until progression or toxicity. Those who were surgical candidates were offered surgical resection of remaining tumor followed by involved-field external beam irradiation to sites of no prior irradiation and intraoperative irradiation to sites of prior external beam irradiation. This trial closed after 36 eligible patients were entered because of poor accrual. Although more than 40% of patients on each arm received fewer than four cycles of MVAC, the clinical response rate was 78% (95% CI: 52-94%) and 50% (95% CI: 26-74%) for MVAC and MVAC + GM-CSF, respectively; the median time to progression was 10.2 and 11.8 months, respectively; and median survival was 13.8 and 16.0 months, respectively. Toxicity was substantial, with more than 40% experiencing grade III to IV leukopenia, and nearly 40% experiencing grade III to IV stomatitis. MVAC with or without GM-CSF support achieves high response rates in patients with advanced, recurrent, or metastatic cervical carcinoma despite dose reductions and deletions. Its progression-free survival and overall survival rates appear promising. These results need to be confirmed within a large randomized phase III clinical trial.

Adult↗
PubMed2002

MR elastography of breast cancer: preliminary results.

OBJECTIVE: Motivated by the long-recognized value of palpation in detecting breast cancer, we tested the feasibility of a technique for quantitatively evaluating the mechanical properties of breast tissues on the basis of direct MR imaging visualization of acoustic waves. SUBJECTS AND METHODS: The prototypic elasticity imaging technique consists of a device for generating acoustic shear waves in tissue, an MR imaging-based method for imaging the propagation of these waves, and an algorithm for processing the wave images to generate quantitative images depicting tissue stiffness. After tests with tissue-simulating phantom materials and breast cancer specimens, we used the prototypic breast MR elastography technique to image six healthy women and six patients with known breast cancer. RESULTS: Acoustic shear waves were clearly visualized in phantoms, breast cancer specimens, healthy volunteers, and patients with breast cancer. The elastograms of the tumor specimens showed focal areas of high shear stiffness. MR elastograms of healthy volunteers revealed moderately heterogeneous mechanical properties, with the shear stiffness of fibroglandular tissue measuring slightly higher than that of adipose tissue. The elastograms of patients with breast cancer showed focal areas of high shear stiffness corresponding to the locations of the known tumors. The mean shear stiffness of breast carcinoma was 418% higher than the mean value of surrounding breast tissues. CONCLUSION: The results confirm the hypothesis that the prototypic breast MR elastographic technique can quantitatively depict the elastic properties of breast tissues in vivo and reveal high shear elasticity in known breast tumors. Further research is needed to evaluate the potential applications of MR elastography, such as detecting breast carcinoma and characterizing suspicious breast lesions.

Adult↗
PubMed2002

Current status of prophylactic mastectomy.

The management of women at high risk for breast cancer presents a clinical dilemma to the health-care provider as well as to the woman herself. Current options include surveillance, prophylactic surgery (mastectomy and/or oophorectomy), and/or chemoprevention. Prophylactic mastectomy, including bilateral prophylactic mastectomy in high-risk women or contralateral prophylactic mastectomy in women with primary breast cancer, has been a controversial clinical option. In this review, we address the efficacy of prophylactic mastectomy in reducing the risk of breast cancer in high-risk women, the use of this procedure, surgical complications, and its psychosocial impact. The decision to undergo prophylactic mastectomy is highly personal and must be preceded by an in-depth assessment of the woman's risk of breast cancer, and a thorough discussion of the benefits of the procedure weighed against its potential surgical risks and psychological impact. It is also imperative that the woman be informed of alternative options for management, including chemoprevention, close surveillance, and prophylactic oophorectomy.

Breast Neoplasms↗
PubMedDate not supplied

Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status.

BACKGROUND: Physical activity is a potentially modifiable breast cancer risk factor. There is considerable recent evidence to suggest that risk factors for breast cancer differ based on its subtype, particularly estrogen receptor (ER)/progesterone receptor (PR) status, but this has been less well studied for physical activity. The objective of this study was to examine the association of physical activity with breast cancer incidence based on ER/PR status of the tumor. METHODS: The Iowa Women's Health Study is a prospective cohort study of 41 836 postmenopausal women. Recreational physical activity was self-reported on the baseline questionnaire, and 3 levels (high, medium, and low) were defined. Breast cancer incidence and ER/PR status, through 18 years of follow-up, were ascertained by linkage with the Iowa Surveillance, Epidemiology, and End Results Cancer Registry. Cox proportional hazards models were used to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer, adjusting for other breast cancer risk factors. RESULTS: During 554 819 person-years of follow-up, 2548 incident cases of breast cancer were observed. Compared with low physical activity, high physical activity levels were inversely associated with risk of breast cancer (RR, 0.86; 95% CI, 0.78-0.96), and there were inverse associations for ER-positive (ER+)/PR-positive (RR, 0.87; 95% CI, 0.75-1.00), ER+/PR-negative (PR-) (RR, 0.67; 95% CI, 0.47-0.96), and ER-negative/PR- (RR, 0.80; 95% CI, 0.56-1.14) tumors. Further adjustment for body mass index attenuated the overall association with breast cancer (RR, 0.91; 95% CI, 0.82-1.01) and for ER+/PR-positive tumors (RR, 0.94; 95% CI, 0.81-1.08), while there was no change for ER+/PR- tumors (RR, 0.66; 95% CI, 0.46-0.94). CONCLUSIONS: Higher recreational physical activity might reduce the risk of postmenopausal breast cancer overall. Risk reduction varies by ER/PR status of the tumor, being most marked for ER+/PR- tumors, which, in general, have been associated with a clinically more aggressive tumor phenotype. If confirmed in additional studies, these results would suggest that additional mechanisms, besides an effect on body mass, may account for observed protective effects of physical activity in reducing breast cancer.

Aged↗