Year Of Breast Cancer Diagnosis Research Articles

Prevalence of women with early-stage breast cancer receiving active management using electronic health records from oncology clinics in the United States.

The purpose of this study was to estimate the prevalence of women receiving treatment or active surveillance for stage I-III breast cancer in the United States from 2009 to 2012, stratified by patient age and tumor characteristics. In each study year, electronic medical records were used to identify women aged ≥18years with stage I-III breast cancer and treated or under active surveillance (≥4 visits) at an oncology clinic that contributes data to the Oncology Services Comprehensive Electronic Records database. Prevalence was projected to the national level overall and within strata (by tumor characteristics, year of breast cancer diagnosis, and age). We identified 5,219 female breast cancer patients (18% <age 50; 58% <age 65) representing 787,082 (95% CI 778,012-796,153) women in the US in 2012. At diagnosis, 44% had stage I, 42% stage II, and 14% stage III disease; 69% had estrogen receptor (ER) and progesterone receptor (PR) expression-positive tumors; 19% were ER- and PR-negative; and 14% had triple-negative phenotype (ER-, PR-, and HER2-negative). Overall 56% of patients received treatment in 2012, 22% chemotherapy, 8% biologic therapy, and 36% endocrine therapy. Treatment prevalence was higher among younger patients and at more advanced disease stages. Approximately half of women with ER-negative, PR-positive, HER2-negative, or triple-negative tumors received chemotherapy. As a conclusion, in 2012, approximately 800,000 women in the US were under treatment or active surveillance for early-stage breast cancer. Treatment prevalence differed by patient age, disease stage, and tumor histology.

Liver metastases from breast cancer: Surgical resection or not? A case-matched control study in highly selected patients

To determine whether, in a highly selected patient population, medical treatment combined with surgical resection of liver metastases from breast cancer is associated with improved survival compared with medical treatment alone. Between 1988 and 2007, 100 liver resections for metastatic breast cancer were performed at Institut Curie, 51 of which met the criteria for inclusion in this case-control study. With the exception of bone metastases, patients with other distant metastasis sites were excluded. Surgery was only performed in patients with stable disease or disease responding to medical treatment evaluated by imaging evaluation. Surgical cases were individually matched with 51 patients receiving medical treatment only. All patients had 4 or fewer resectable liver metastases. The study group was matched with the control group for age, year of breast cancer diagnosis, time to metastasis, TNM stage, hormone receptor status and breast cancer tumour pathology. Univariate analysis confirmed a survival advantage for patients lacking bone metastases and axillary lymphadenopathy at the time of breast cancer diagnosis and for surgically treated patients. Multivariate analysis indicated that surgery and the absence of bone metastases were associated with a better prognosis. A multivariate Cox model adapted for paired data showed a RR=3.04 (CI: 1.87-4.92) (p<0.0001) in favour of surgical treatment. Surgical resection of liver metastases from primary breast cancer appears to provide a survival benefit for highly selected patients.

Weight change in patients with treatment of breast cancer.

127 Background: Studies have shown that breast cancer (BC) treatment can increase weight (wt). Wt gain during chemotherapy is usually significant and maybe associated with poor survival. Role of current treatment regimens and wt gain is not reviewed. Methods: We retrospectively analyzed the mean percentage (%) wt change during the 1st year following BC diagnosis in 246 patients (pts) between Sept 2007 and Oct 2010. Kruskal-Wallis test and post-hoc pairwise comparisons were used to assess the influence of various factors including age, histology, stage, ER/PR/HER-2/neu status, menopausal status and types of therapeutic modalities received on the % wt change. Kaplan-Meier method with log-rank test was used to evaluate recurrence free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free pts were censored at last follow-up. Results: Mean wt gain was 0.39% (±0.40) at 1 year from diagnosis of BC. Premenopausal status was the only factor associated with significant wt gain (+1.67% vs. -0.10% for postmenopausal pts; p=0.02). Stage ≥ III was associated with significant wt loss (-1.64% for III/IV vs. +0.85% for 0/I/II; p=0.02) and a lower RFS at 3yrs and 5yrs (p&lt; 0.0001). Higher baseline wt (&gt;90th percentile) did not have any significant impact on RFS at 3 years (0.84 vs. 0.91; p=0.19). There was no significant change in wt relative to other factors as shown in Table. Conclusions: Our study using current treatment regimens did not show any significant change in % wt with chemotherapy during the 1st year of BC diagnosis. Premenopausal status was the only factor associated with significant wt gain while stage ≥ III was associated with significant wt loss and lower RFS. [Table: see text]

Effect of adjuvant bisphosphonates on disease-free survival in early breast cancer: Retrospective analysis results in an unselected single-center cohort

Bisphosphonates are the gold standard for preventing skeletal-related events in patients with bone-metastatic cancer and have been investigated for reducing cancer treatment-induced bone loss. Evidence suggests bisphosphonates also offer anticancer benefits in adjuvant and advanced cancer settings. We conducted a retrospective analysis of data from a single-center, unselected cohort of women with early breast cancer (N=1646: 962 received adjuvant bisphosphonates, 684 did not) to assess the impact of bisphosphonates on disease-free and overall survival. The bisphosphonate group comprised all women who started bisphosphonate treatment within 1 year of breast cancer diagnosis and received ≥3 months of bisphosphonate treatment (zoledronic acid, clodronate, ibandronate, or alendronate; majority received zoledronic acid). Disease-free survival was defined as the time from breast cancer diagnosis until first disease recurrence or death. Treatment groups were balanced for cancer stage, hormone receptor expression, and human epidermal growth factor receptor-2 expression. Patients in the no-bisphosphonate group were more likely to be ≥75 years of age, node-negative, and have histologic grade 3 tumors. In patients treated with adjuvant bisphosphonates, disease-free survival was significantly longer than in those who did not receive bisphosphonates (P=0.0017). Both disease-free and overall survival were significantly longer in patients with hormone receptor-positive disease irrespective of lymph node status (disease-free survival: P=0.0038; overall survival: P<0.0026). No significant disease-free survival difference was detected in patients with hormone receptor-negative disease. This large, retrospective study demonstrates a significant survival benefit with adjuvant bisphosphonates in patients with early breast cancer, particularly in patients with node-positive and hormone receptor-positive disease.

Outcomes of 47 patients with human immunodeficiency virus infection treated for breast cancer: A 20-year experience.

1071 Background: Patients (pts) with Human Immunodeficiency Virus (HIV) are living longer and non-AIDS defining malignancies have been increasingly reported in these patients. Methods: Retrospective review identified 47 pts with breast cancer (BC) and HIV who were seen at the University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital between January 1999 and June 2011. Results: Pt characteristics: 46 female, 1 male, mean age 46 years (range 31-65). Race: African American 79%, Caucasian 21%. Ethnic: Hispanics 14%, non-Hispanics 86%. Premenopausal 68% postmenopausal 32%. Tumor characteristics: Stage: Tis 4%, Stage I: 6 % , Stage II: 38%, Stage III: 38%, Stage IV: 9%. ER positive (50%) her-2 positive (15%), Triple negative (21%). HIV characteristics: 36 pts with HIV before or concurrent with the diagnosis of BC. 6 pts diagnosed with HIV within 1 year of BC diagnosis. HIV dx date unavailable in 5 pts. 27% had AIDS. CD4 counts (in cells/µL)were: &gt; 500 (23%); 201-500 (37%), 51 – 200 (20%) &lt; 50 (20%). 15 pts were diagnosed with BC in preHAART era. Of those dx with BC after 1996, 60% were on HAART. BC treatment: 43 pts had localized disease. 32 underwent modified radical mastectomy, 8 breast conservation and 3 pts refused surgery. 26 pts received curative or palliative chemotherapy. Complications of BC treatment: serious side effects were reported in 11 (42%) including neutropenic fever/sepsis (10 pts), ARDS (1 pt). Zoster infection was reported in 12% of the pts. 3 patients developed rapidly progressive and fatal AIDS within 6 months of completion of chemotherapy. Survival: See Table. Conclusions: BC in patients with HIV infection spans the spectrum of BC presentations. Hormonal therapy, surgery and radiation therapy were well tolerated. Infectious complications were common in patients treated with chemotherapy and routine use of growth factors and prophylactic acyclovir should be considered. [Table: see text]

Risk of Primary Non–Breast Cancer After Female Breast Cancer by Age at Diagnosis

Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment alters the risk pattern by age. We identified 304,703 women diagnosed with breast cancer during 1943 to 2006 in the Cancer Registries of Denmark, Norway, and Finland. Relative risks (RR) of subsequent non-breast cancer by age at cancer diagnosis were calculated using Poisson regression models adjusted for country, calendar period, length of follow-up, and treatment. Excess absolute risks (EAR) were also calculated. The RR for all cancer sites except breast cancer decreased with increasing age both with and without adjustments. The RR and the EAR differed for each age at diagnosis category until the women reached their late 70s. Many specific cancer forms contributed to the overall risk pattern by age with endometrial cancer as 1 exception. The age at breast cancer diagnosis is an essential risk factor for being diagnosed with a new primary non-breast cancer and the level of risk for specific ages at diagnosis may hold for many years after the diagnosis. Occurrence of endometrial cancer after breast cancer seems to follow a distinct age pattern different from that seen for most other cancer types. Future studies should aim at exploring the underlying explanations for the age-related findings.

Characteristics and Outcomes of Breast Cancer in Women With and Without a History of Radiation for Hodgkin's Lymphoma: A Multi-Institutional, Matched Cohort Study

To compare characteristics and outcomes of breast cancer in women with and without a history of radiation therapy (RT) for Hodgkin's lymphoma (HL). Women with breast cancer diagnosed from 1980 to 2006 after RT for HL were identified from eight North American hospitals and were matched three-to-one with patients with sporadic breast cancer by age, race, and year of breast cancer diagnosis. Information on patient, tumor and treatment characteristics, and clinical outcomes was abstracted from medical records. A total of 253 patients with breast cancer with a history of RT for HL were matched with 741 patients with sporadic breast cancer. Median time from HL to breast cancer diagnosis was 18 years. Median age at breast cancer diagnosis was 42 years. Breast cancer after RT for HL was more likely to be detected by screening, was more likely to be diagnosed at an earlier stage, and was more likely to be bilateral at diagnosis. HL survivors had an increased risk of metachronous contralateral breast cancer (adjusted hazard ratio [HR], 4.3; 95% CI, 1.7 to 11.0) and death as a result of any cause (adjusted HR, 1.9; 95% CI, 1.1 to 3.3). Breast cancer-specific mortality was also elevated, but this difference was not statistically significant (adjusted HR, 1.6; 95% CI, 0.7 to 3.4). In women with a history of RT for HL, breast cancer is diagnosed at an earlier stage, but these women are at greater risk for bilateral disease and are more likely to die as a result of causes other than breast cancer. Our findings support close follow-up for contralateral tumors in these patients and ongoing primary care to manage comorbid conditions.

PS3-18: Use of Antidepressant and Anti-Anxiety Medications Among Breast Cancer Survivors in a HMO

Background: Almost 200,000 U.S. women are diagnosed each year with breast cancer and over 40,000 women will die of the disease. In addition to the medical and functional consequences of the diagnosis and treatment, women experience worry, persistent anxiety, fear and depressive disorders. Overall, 30% of women diagnosed with breast cancer suffer significant distress at some point in their illness trajectory. National health organizations including the Institute of Medicine and National Cancer Institute call for treatment of common symptoms among breast cancer patients such as depression and anxiety. To date, there are only limited reports on the prevalence of treatment, and even fewer studies have examined potential differences by race/ethnicity, age, or tumor characteristics. Aim: To describe the prevalence of pharmacotherapy for depressive symptoms/anxiety among patients diagnosed with breast cancer in a large HMO. Methods: We identified all women diagnosed with primary breast cancer between 2000–2006 (n=10,408) who had been members of Kaiser Permanente Southern California (KPSC) for 1+ years prior to diagnosis. KPSC is a nonprofit comprehensive prepaid health plan serving 3.2 million socioeconomically diverse members. Data was obtained from the KPSC SEER-affiliated cancer registry and automated clinical, pharmacy, and membership databases. We examined patient and tumor characteristics associated with new use of pharmacotherapy for depression/anxiety. Univariate odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Results: We found 35% of women (3,611 of 10,408) were newly prescribed either anti-depressant or anti-anxiety medications within a year of breast cancer diagnosis. Younger women (e.g., OR=1.44, CI=1.28–1.63 for 40–49 year olds v. 60–69) and women with higher stage (e.g., OR=3.40, CI=2.87–4.04 for Stage 3 v. Stage 0) were more likely to be prescribed these medications, while African-American (OR=0.81, CI=0.72–0.92) and Asian-Pacific Islander (0.73, CI=0.64–0.84 women were less likely compared to non-Hispanic white women. Conclusions: While future research needs to determine the number of breast cancer survivors screened and diagnosed with depression/anxiety, results of pharmacotherapy utilization in this insured population are consistent with national reports of the prevalence of psychosocial distress experienced after breast cancer diagnosis. Potential age and race/ethnicity disparities are of concern and need further study.

Breast Cancer Surgery Trend Changes Since the Introduction of BRCA1/2 Mutation Screening: A Retrospective Cohort Analysis of 158 Mutation Carriers Treated at a Single Institution

Bilateral mastectomy in women diagnosed with unilateral breast cancer is on the rise in the USA. One contributing factor is increased awareness of contralateral breast cancer risk. Positive testing for deleterious mutation in BRCA1/2 is a concrete measure of this contributing factor. We hypothesize that breast cancer surgery trend change is temporally associated with the introduction of BRCA1/2 genetic testing around 1996. Our study cohort included 158 BRCA1 or BRCA2 mutation carriers diagnosed with unilateral breast cancer between 1963 and 2009. Mutation carriers with ovarian cancer or bilateral breast cancer were excluded. Breast surgery and breast reconstruction surgery trends were analyzed according to year of breast cancer diagnosis or when bilateral mastectomy was performed, respectively. Surgery trends changed significantly over time. We observed a significant drop in the rate of unilateral mastectomy (P<0.001) after the period 1996-2000, and the rate of bilateral mastectomy appears to be on the rise, up to 30.3% between 2006 and 2009. Breast reconstruction trends also changed significantly over time, with a significant rise in the rate of free flap reconstruction to 58.8% between 2006 and 2009. Our results demonstrated a significant decrease in unilateral mastectomy with a rise in bilateral mastectomy after the period 1996-2000, a period which encompassed the year when genetic testing of the two BRCA1/2 genes became commercially available, hence supporting our hypothesis.

Treatment with antidepressant and anti-anxiety medications after breast cancer diagnosis in a large HMO.

9045 Background: 30% of the 200,000 U.S. women diagnosed each year with breast cancer (BCa) suffer significant distress at some point in their illness trajectory. Beyond medical and functional consequences of the diagnosis and treatment, women experience worry, persistent anxiety, fear and depressive disorders. The Institute of Medicine and National Cancer Institute call for treatment of common symptoms such as depression and anxiety among BCa survivors, yet there are only limited reports on the prevalence of treatment, and even fewer studies have examined potential differences by race/ethnicity, age, or tumor characteristics. Methods: We identified all women diagnosed with primary BCa between 2000-2006 who were members of Kaiser Permanente Southern California (KPSC) for 1+ years and who had not been treated for depression/anxiety in the year prior to diagnosis (n = 10,408). KPSC is a nonprofit prepaid health plan serving 3.3 million socioeconomically diverse members. Data were obtained from the KPSC SEER-affiliated cancer registry and automated clinical, pharmacy, and membership databases. We examined patient and tumor characteristics associated with new use of pharmacotherapy for depression/anxiety. Overall odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Results: 35% of women were newly prescribed either anti-depressant or anti-anxiety medications within a year of BCa diagnosis. Younger women (e.g., OR = 1.44, CI = 1.28-1.63 for 40-49 year olds vs. 60- 69 year olds) and women with higher stage (e.g., OR = 3.40, CI = 2.87-4.04 for Stage 3 vs. Stage 0) were more likely to receive these treatments. African-American (OR = 0.81, CI = 0.72-0.92) and Asian-Pacific Islander (0.73, CI = 0.64-0.84) women were less likely to be prescribed medications compared to non- Hispanic white women. Conclusions: Pharmacotherapy utilization in this insured population is consistent with national reports of the prevalence of psychosocial distress experienced after BCa diagnosis. Future research needs to examine the number of BCa survivors screened and diagnosed with depression/anxiety. Potential age and race/ethnicity disparities are of concern and need further study. No significant financial relationships to disclose.

Histological Characterization of 47 Breast Cancers with Neoplastic Meningitis Evolution.

Abstract IntroductionAround 5% of patients with breast cancer develop neoplastic meningitis (NM). The prognosis of NM in this population is supposed to be better with a median survival time of 7 months if treated with intrathecal therapy, systemic treatment and adapted supportive care (versus 4-6 weeks if untreated). This evolution needs to be detected as early as possible and it is necessary to identify tumors with such a risk. We report histological characteristics in 47 breast cancers with leptomeningeal treated in our institution for the last 2 years.Aim of the studyTo identify histopathological characteristics of breast cancer predictive of leptomeningeal evolution.Patients and methods47 consecutive female breast cancer patients were diagnosed with neoplastic meningitis on the basis of cerebrospinal fluid (CSF) cytology and/or cerebrospinal MRI plus clinical symptoms. These patients were matched with 47 breast cancer's patients without leptomeningeal evolution, according to age at breast cancer diagnosis (+/- 2 years), year of breast cancer diagnosis (+/- 2 years) and use of systemic chemotherapy as initial treatment of breast cancer. Differences between the 2 groups of patients were analyzed using usual statistical methods (t-test, Chi square test).ResultsAt the time of NM diagnosis, the median (min-max) age of patients with NM was 51 (26-76) years. Median delay after breast cancer diagnosis was 33 months (0-193). Brain, hepatic, bone, lung metastases were present in respectively 47%, 43%, 47% and 19%. CSF cytology was positive in 72%, median proteinorachia was 0,75 g/l (0,17–16,12); cerebrospinal MRI was also positive in 87%. At the time of breast cancer, median age was 49 (25-70) years. Initial breast samples were tumor biopsy in 43%, partial mastectomy in 31% and total mastectomy in 27%. Breast tumors were invasive ductal carcinoma in 84% with histoprognostic grade II/III in 49/42%, MSBR grade I/II in 52/47%. Grade 3 of differentiation was observed in 68%, grade 3 of anisonucleosis in 59% and grade 1 of mitosis in 48%. In the tumors, estrogen/progesterone receptors (ER/PR) were detected in 67/48% and HER2 overexpression was observed in 24%. 19% of the tumors were triple negative. Vascular emboli were detected in 58% of the cases. Tumors were T2 in 43%, N+ in 66% and M+ in 14%. Significant differences between initial breast cancers with or without NM evolution concerned histological type (p = 0,043), ER (p = 0,004) and PR (p = 0,023), triple negative status (p = 0,009) and initial metastatic status (p &amp;lt; 0,007).ConclusionsCarcinomatous meningitis preferentially occurs in invasive lobular tumors without hormonal receptors, particularly in triple negative tumors and in tumors metastatic upfront. HER2 overexpression is not a risk factor of NM, as is observed with brain metastases. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6013.

Latent class modelling of the association between socioeconomic background and breast cancer survival status at 5 years incorporating stage of disease

BackgroundStage of disease and socioeconomic background (SEB) are often used to ‘explain’ differences in breast cancer outcomes. There are challenges for all types of analysis (eg, survival analysis, logistic regression),...

Secondary Causes of Low Bone Mass in Patients With Breast Cancer: A Need for Greater Vigilance

An observational study to assess the prevalence of secondary causes of low bone density in patients with breast cancer. Female patients within 5 years of breast cancer diagnosis and age older than 50 years at diagnosis were recruited. Consenting patients completed a questionnaire and had blood taken for serum calcium, vitamin D, parathyroid hormone (PTH), and thyroid function testing. Bone mineral density (BMD) was assessed. Abnormalities were additionally investigated and treated. Two hundred patients were recruited. The median age at diagnosis was 62 years. One hundred sixty-nine patients had hormone receptor (HR) -positive cancer. Vitamin D and thyroid function were assessed in 200 patients; PTH was assessed in 197 patients; and BMD was assessed in 187 patients. Eighty-seven patients (46.5%) had osteopenia, and 24 patients (12.8%) had osteoporosis. Vitamin D levels were insufficient (ie, 50 to 75 nmol/L) in 74 patients (37%) and were deficient (ie, < 50 nmol/L) in 54 patients (27%). Only 24 of 65 patients taking vitamin D supplements were replete (ie, > 75 nmol/L). Thirty-nine (21%) of 197 patients had PTH concentrations greater than the normal range. Six had primary hyperparathyroidism (PHPT), and two more had recent surgery for PHPT. Twenty-seven had secondary hyperparathyroidism (HPT) from vitamin D deficiency and six had normocalcemic HPT. Of 90 patients with low BMD and HR-positive cancer, 8% (seven of 90 patients) had new or recent PHPT, and 63% (57 of 90 patients) had insufficient or deficient vitamin D. More patients with HR-positive cancer than with HR-negative cancer had elevated PTH (38 of 167 v three of 30 patients, respectively; P = .10). Secondary causes of low BMD are common in postmenopausal women. Identification and management of secondary causes should be included in bone health management algorithms.

Synchronous and metachronous bilateral breast cancer: Are the risks greater in women with a history of radiation for Hodgkin lymphoma?

607 Background: Women with a history of radiation therapy (RT) for Hodgkin lymphoma (HL) have an elevated risk of breast cancer (BC). The characteristics, treatment and outcomes of these cancers, compared with sporadic breast cancers, are not well described. In particular, rates of synchronous and metachronous bilateral BC may be greater in patients with a history of RT for HL. Methods: Women diagnosed with BC between 1980 and 2006 following RT for HL were identified retrospectively from 8 institutions in North America. Each patient in this cohort was matched with 3 BC patients with no history of HL, from the same institution, by age at BC diagnosis, year of BC diagnosis and race. Information on patient and tumor characteristics, disease recurrence and new contralateral tumors was obtained from medical records. Analysis of metachronous contralateral breast cancer (CBC) was limited to women with a breast at risk, and adjusted hazard ratios (HRs) for CBC were estimated using Cox proportional hazards regression. Results: 253 BC patients with a history of RT for HL were matched with 741 patients with sporadic BC. The median interval between HL and first BC diagnosis was 19 years. Median age at BC diagnosis was 44 years and median follow-up was 5 years from BC diagnosis. Synchronous bilateral BC was diagnosed in 6% of the HL survivors and 2% of the matched patients with sporadic BC. Among women with unilateral disease, 21% of HL survivors and 3% of sporadic BC patients had a bilateral mastectomy. Overall 64 women with a breast at risk developed metachronous CBC. BC patients with a history of RT for HL had a greater rate of metachronous CBC (adjusted hazard ratio 3.3, 95% CI 2.1–5.8), controlling for patient, tumor and treatment characteristics. In addition, those who received chemotherapy for BC were less likely to develop CBC (adjusted HR 0.51, 95% CI 0.31–0.85), and those with a family history of BC in a 1st degree relative were more likely to develop CBC (adjusted HR 1.8, 95% CI 1.1–3.0). Conclusions: Women who develop BC after RT for HL have more than 3 times the risk of CBC than similar women with sporadic BC. Our findings support close follow-up for CBC in BC patients with a history of RT for HL and may inform decisions about prophylactic mastectomy in this population. No significant financial relationships to disclose.

Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer

Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk. We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC >or= 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC. Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC. PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.

Leukemia following breast cancer: an international population-based study of 376,825 women

To quantify long-term temporal trends in the excess absolute risk (EAR) of secondary leukemia among breast cancer (BC) survivors, using multivariate analyses to evaluate the effects of subtype, age at BC diagnosis, attained age, and calendar year. We identified 376,825 1-year survivors of BC within 4 nationwide, population-based cancer registries in Sweden, Denmark, Finland, and Norway (1943-2001). Estimates of EAR (per 100,000 person-years) were modeled using Poisson regression methods and cumulative risks calculated using a competing risk model. A total of 687 non-chronic lymphocytic leukemias (EAR = 9.05; 95% confidence interval (CI) = 7.5-10.7) was reported. Significantly elevated risks were observed for the first time for chronic myeloid leukemia (CML) (EAR = 2.06; 95% CI = 1.3-2.9) and acute lymphoblastic leukemia (ALL) (EAR = 0.62; 95% CI = 0.2-1.1), in addition to acute myeloid leukemia (AML) (EAR = 5.00; 95% CI = 3.9-6.2). Excesses of CML, ALL, AML and all leukemias combined persisted over 25 years after BC diagnosis. For all leukemias, EAR decreased with increasing calendar year (P = 0.04) of BC diagnosis. Risk for all leukemia and AML by calendar year of BC diagnosis depended on age at diagnosis. For women diagnosed with BC after 1985, the 10-year cumulative risk of leukemia for those diagnosed before and after age 50 was small, 0.10% and 0.14%, respectively. Although secondary leukemia is a rare event, BC survivors experience statistically significant excesses for at least 25 years after diagnosis, including CML and ALL. Decreasing leukemia risks in recent calendar years likely reflect changes in treatment.

Rural–urban differences in the presentation, management and survival of breast cancer in Western Australia

From all women diagnosed with invasive breast cancer in 1999 in Western Australia, rural and urban women were compared with regard to mode of detection, tumour characteristics at presentation, diagnostic investigations, treatment and survival. Women from rural areas with breast cancer (n=206, 23%) were less likely to have open biopsy with frozen section (P<0.001), breast-conserving surgery (P<0.001), adjuvant radiotherapy (P=0.004) and hormonal therapy (P=0.03), and were less likely to be treated by a high caseload breast cancer surgeon (P<0.001). Adjusting for age and tumour characteristics, rural women had an increased likelihood of death within 5 years of breast cancer diagnosis (HR 1.62, 95% CI 1.10-2.38). This difference was not significant after adjustment for treatment factors (HR 1.36, 95% CI 0.90-2.04).

Screening Clinical Breast Examination: How Often Does It Miss Lethal Breast Cancer?

Although most American women regularly receive screening clinical breast examination (CBE), little is known about CBE accuracy in community practice. We sought to estimate the rate of cancer detection (sensitivity) of screening CBE performed by community-based clinicians on women who ultimately died of breast cancer, as well as to identify factors associated with accurate detection. We evaluated CBE accuracy among asymptomatic female health plan enrollees in five states (WA, OR, CA, MA, and MN) who received a CBE within 1 year of breast cancer diagnosis and who died of breast cancer within 15 years of diagnosis (N = 485). Sensitivity was estimated as the proportion whose exam was abnormal. Bivariate and logistic regression analyses identified patient characteristics associated with cancer detection. An abnormality was noted on screening CBE in one of five women who ultimately succumbed to breast cancer (sensitivity = 21.6%; 95% confidence interval [CI] = 18.1% to 25.6%). The odds of a true-positive screening CBE (sensitivity) were decreased among women using estrogen (odds ratio [OR] = 0.23; 95% CI = 0.07 to 0.80), receiving a Pap smear during the same visit as CBE (OR = 0.45; 95% CI = 0.27 to 0.72), and with increasing chronic disease comorbidity (P(trend) = .08). Screening CBE as performed in the community may be insufficiently sensitive to detect most lethal breast cancers. Low sensitivity of screening CBE in community practice may be partly attributable to its performance alongside time-consuming clinical tasks such as Pap smear screening or chronic illness care.

Stroke Risk and Tamoxifen Therapy for Breast Cancer

Tamoxifen, which is used widely to treat, and increasingly to prevent, breast cancer, has been associated with increased risk of stroke. We assessed the impact of tamoxifen treatment for breast cancer on the risk of stroke, considering dose, duration, and recency of use of tamoxifen and known stroke risk factors. We conducted a nested case-control study of stroke after breast cancer among female Los Angeles County residents enrolled in a large health maintenance organization when diagnosed with breast cancer between January 1, 1980, and July 1, 2000. We obtained information on breast cancer treatment and stroke risk factors through medical record review and telephone interviews. The association (odds ratio [OR] and 95% confidence interval [CI]) between tamoxifen and stroke risk was determined by using a conditional logistic regression model, adjusting for menopausal status and history of hypertension and diabetes. All statistical tests were two-sided. Of 11 045 women with breast cancer, 179 met stroke eligibility criteria and were individually matched to two stroke-free control subjects with breast cancer on age and year of breast cancer diagnosis. The mean age at breast cancer diagnosis was 66.6 years (standard deviation [SD] = 12.3 years), and the mean at-risk period (i.e., the time between breast cancer diagnosis and first stroke or comparable time period for control subjects) was 5.7 years (SD = 4.5 years). Tamoxifen use was not associated with risk of stroke, either overall (OR = 1.0, 95% CI = 0.6 to 1.6) or in subgroups defined by duration, dose, or recency of use. Chemotherapy, but not a specific chemotherapy regimen, was associated with an increased risk of stroke, regardless of tamoxifen use (no tamoxifen use, OR = 2.8, 95% CI = 1.3 to 6.3; tamoxifen use OR = 2.2, 95% CI = 1.2 to 4.1). Tamoxifen use is not associated with increased stroke risk. Further exploration of possible increased stroke risk following chemotherapy treatment for breast cancer is needed.

Lung cancer risk and radiation dose among women treated for breast cancer.

Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose. This study evaluated the long-term risk of lung cancer among women treated with radiation for breast cancer. In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high-dose cell killing or the fractionated nature of the exposure. Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10,000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects.