Persistence of patient-detected breast cancer over time: 1990-2019.

BACKGROUND: The continued presentation of patient-detected breast cancer (BC) and associated characteristics over time is understudied. METHODS: In a large institutional cohort of first primary stage 0-IV patients with BC in 1990-2019 (n = 15,827), diagnostic method (patient-detected [PtDBC] [n = 5844]; mammography-detected [MamDBC] [nondiagnostic] [n = 9248]; and physician-detected [PhysDBC] [n = 736]) and patient and tumor characteristics including age, race, TNM stage, and hormone-receptor status were reviewed. Pearson χ2 tests for bivariate comparisons and logistic regression for patient detection-associated factors were used. RESULTS: In a cohort from 1990 to 2019, the proportion aged 50-74 years (55%-63%; p < .001) and non-White race (9%-37%; p < .001) increased over time. Percentage PtDBC decreased over time but case numbers increased (1990-1999: 44% [n = 1399]; 2010-2019: 34% [n = 2349]; p < .001). Excluding stage 0, PtDBC declined from 47% to 41% over time (p < .001). In 2010-2019, 21% of cases were stage 0, 91% of which were mammography detected (n = 1439). Seventy percent of patient-detected cases were stage II-IV (stage II, 44%; stage III, 20%; stage IV, 6%; p < .001). In adjusted logistic regression, the odds of PtDBC decreased over time (2000-2009: odds ratio [OR], .65 [95% CI, .58-.72]; 2010-2019: OR, .54 [95% CI, .49-.60]), with age <40 years OR, 15.81, and Black and non-White other at 50% increased risk. CONCLUSIONS: The relative proportion of PtDBC decreased to a constant 34%-40% of total cases after 1990-1999. PtDBC case numbers increased in subsequent years (2000-2019), and were consistently higher stage. Interval cancers, mammography-screening uptake, breast health awareness of age groups outside screening guidelines, and underserved socioeconomic groups may be related to the continued significant PtDBC incidence. PLAIN LANGUAGE SUMMARY: After decades of mammography-screening availability, symptomatic patient-detected breast cancer declined over time from 44% to a persistent rate of 34% in our institutional cohort. The persistence of patient-detected breast cancer over time presents a difficult situation for patients and care givers without clear diagnosis pathways for younger and older women outside recommended screening guidelines, who often present with higher stage and more lethal characteristics. More timely diagnosis and treatment including breast health awareness, prompt presentation of breast problems, outreach to younger age and minority groups, and provision of specialized training and care delivery for symptomatic patient-detected breast cancer are needed.

COVID-19 related change in breast cancer diagnosis, stage, treatment, and case volume: 2019-2021.

PURPOSE: Evaluate the COVID-19 pandemic impact on breast cancer detection method, stage and treatment before, during and after health care restrictions. METHODS: In a retrospective tertiary cancer care center cohort, first primary breast cancer (BC) patients, years 2019-2021, were reviewed (n = 1787). Chi-square statistical comparisons of detection method (patient (PtD)/mammography (MamD), Stage (0-IV) and treatment by pre-pandemic time 1: 2019 + Q1 2020; peak-pandemic time 2: Q2-Q4 2020; pandemic time 3: Q1-Q4 2021 (Q = quarter) periods and logistic regression for odds ratios were used. RESULTS: BC case volume decreased 22% in 2020 (N = 533) (p = .001). MamD declined from 64% pre-pandemic to 58% peak-pandemic, and increased to 71% in 2021 (p < .001). PtD increased from 30 to 36% peak-pandemic and declined to 25% in 2021 (p < .001). Diagnosis of Stage 0/I BC declined peak-pandemic when screening mammography was curtailed due to lock-down mandates but rebounded above pre-pandemic levels in 2021. In adjusted regression, peak-pandemic stage 0/I BC diagnosis decreased 24% (OR = 0.76, 95% CI: 0.60, 0.96, p = .021) and increased 34% in 2021 (OR = 1.34, 95% CI: 1.06, 1.70, p = .014). Peak-pandemic neoadjuvant therapy increased from 33 to 38% (p < .001), primarily for surgical delay cases. CONCLUSIONS: The COVID-19 pandemic restricted health-care access, reduced mammography screening and created surgical delays. During the peak-pandemic time, due to restricted or no access to mammography screening, we observed a decrease in stage 0/I BC by number and proportion. Continued low case numbers represent a need to re-establish screening behavior and staffing.

Trastuzumab therapy duration in HER2-positive de novo metastatic breast cancer: 1999-2018.

PURPOSE: The optimal duration of first-line trastuzumab (T) treatment for de novo stage IV HER2-positive metastatic breast cancer (MBC) patients after complete response (CR) is not known. METHODS: A retrospective cohort study of de novo stage IV HER2-positive MBC patients who had trastuzumab included in their initial treatment (n = 69), 1999-2018, was conducted with follow-up for CR, progressive disease (PD), vital status, and disease-specific survival (DSS). Statistics included Kaplan-Meier plots and Cox proportional hazards models. RESULTS: Mean trastuzumab treatment time was 4.1 years (range 0.1-15). 54% of patients experienced CR at average time 9 months on treatment (n = 37). Eight CR patients discontinued T treatment after 18 months average post-CR time (range 0-86) and twenty-nine stayed on T treatment post CR [average 65 months (range 10-170)]. Average follow-up was 6 years, range 1-15 years. 5-year DSS was 92% for CR on T patients (N = 29); 88% CR off T (n = 8); 73% No CR on T (n = 14); and 29% No CR off T (n = 18) (p < 0.001). In forward Cox proportional hazards modeling, CR = yes [HzR = 0.31, (95% CI 0.14, 0.73), p = 0.007], continuous T treatment > 2 years [HzR = 0.24, (95% CI 0.10, 0.62), p = 0.003], and age < 65 [HzR = 0.29, (95% CI 0.11, 0.81), p = 0.018] were significantly associated with better DSS. CONCLUSION: Maximum trastuzumab treatment time to CR was 27 months with 2 or more years trastuzumab treatment independently associated with better survival. Survival comparisons and hazard modeling both indicate as good or better survival associated with continuous trastuzumab treatment regardless of CR status. Word count (n = 250).

Breast cancer distant recurrence lead time interval by detection method in an institutional cohort.

BACKGROUND: Lead time, the interval between screen detection and when a disease would have become clinically evident, has been cited to explain longer survival times in mammography detected breast cancer cases (BC). METHODS: An institutional retrospective cohort study of BC outcomes related to detection method (mammography (MamD) vs. patient (PtD)). Cases were first primary invasive stage I-III BC, age 40-74 years (n = 6603), 1999-2016. Survival time was divided into 1) distant disease-free interval (DDFI) and 2) distant disease-specific survival (DDSS) as two separate time interval outcomes. We measured statistical association between detection method and diagnostic, treatment and outcome variables using bivariate comparisons, Cox proportional hazards analyses and mean comparisons. Outcomes were distant recurrence (n = 422), DDFI and DDSS. RESULTS: 39% of cases were PtD (n = 2566) and 61% were MamD (n = 4037). MamD cases had a higher percentage of Stage I tumors [MamD 69% stage I vs. PtD 31%, p < .001]. Rate of distant recurrence was 11% among PtD BC cases (n = 289) vs. 3% of MamD (n = 133) (p < .001). Order of factor entry into the distant recurrence time interval (DDFI) model was 1) TNM stage (p < .001), 2) HR/HER2 status (p < .001), 3) histologic grade (p = .005) and 4) detection method (p < .001). Unadjusted PtD DDFI mean time was 4.34 years and MamD 5.52 years (p < .001), however when stratified by stage, the most significant factor relative to distant recurrence, there was no significant difference between PtD and MamD BC. Distant disease specific survival time did not differ by detection method. CONCLUSION: We observed breast cancer distant disease-free interval to be primarily associated with stage at diagnosis and tumor characteristics with less contribution of detection method to the full model. Patient and mammography detected breast cancer mean lead time to distant recurrence differed significantly by detection method for all stages but not significantly within stage with no difference in time from distant recurrence to death. Lead time difference related to detection method appears to be present but may be less influential than other factors in distant disease-free and disease specific survival.

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders.

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain. IMPLICATIONS FOR PRACTICE: Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

Metastatic breast cancer survival improvement restricted by regional disparity: Surveillance, Epidemiology, and End Results and institutional analysis: 1990 to 2011.

BACKGROUND: The extent of breast cancer outcome disparity can be measured by comparing Surveillance, Epidemiology, and End Results (SEER) breast cancer-specific survival (BCSS) by region and with institutional cohort (IC) rates. METHODS: Patients who were diagnosed with a first primary, de novo, stage IV breast cancer at ages 25 to 84 years from 1990 to 2011 were studied. The change in 5-year BCSS over time from 1990 to 2011 was compared using the SEER 9 registries (SEER 9) without the Seattle-Puget Sound (S-PS) region (n = 12,121), the S-PS region alone (n = 1931), and the S-PS region IC (n = 261). The IC BCSS endpoint was breast cancer death confirmed from chart and/or death certificate and cause-specific survival for SEER registries. BCSS was estimated using the Kaplan-Meier method. Hazard ratios (HzR) were calculated using Cox proportional-hazards models. RESULTS: For SEER 9 without the S-PS region, 5-year BCSS improved 7% (from 19% to 26%) over time, it improved 14% for the S-PS region (21% to 35%), and it improved 27% for the S-PS IC (29% to 56%). In the IC Cox proportional-hazards model, recent diagnosis year, chemotherapy, surgery, and age <70 years were associated with better survival. For SEER 9, additional significant factors were white race and positive hormone receptor status and S-PS region was associated with better survival (HzR, 0.87; 95% CI, 0.84-0.90). In an adjusted model, hazard of BC death decreased in the most recent time period (2005-2011) by 28% in SEER 9 without S-PS, 43% in the S-PS region and 45% in the IC (HzR, 0.72 [95% CI, 0.67-0.76], 0.57 [95% CI, 0.49-0.66], and 0.55 [95% CI, 0.39-0.78], respectively). CONCLUSIONS: Over 2 decades, the survival of patients with metastatic breast cancer improved nationally, but with regional survival disparity and differential improvement. To achieve equitable outcomes, access and treatment approaches will need to be identified and adopted.

Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990-2010.

BACKGROUND: Differences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described. METHODS: A retrospective cohort study, 1990-2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distant metastatic recurrence (stage I-III initial diagnosis) [dnMBC = 247, rMBC = 911)]. Analysis included Chi squared tests of categorical variables, Kaplan-Meier survival estimates, and Cox proportional adjusted hazard ratios (HzR) and 95% confidence intervals (CI). Disease specific survival (DSS) was time from diagnosis or distant recurrence to BC death. RESULTS: Over time, 1990-1998, 1999-2004, and 2005-2010, dnMBC incidence was constant (3%) and rMBC incidence decreased [18% to 7% (p < 0.001)] with no change in dnMBC hormone receptor (HR) or her2-neu (HER2) status but a decrease in rMBC HER2-positive cases and increase in triple negative breast cancer (HR-negative/HER2-negative) (p = 0.049). Five-year dnMBC DSS was 44% vs. 21% for rMBC (p < 0.001). Five-year dnMBC DSS improved over time [28% to 55% (p = 0.008)] and rMBC worsened [23% to 13%, p = 0.065)]. Worse DSS was associated with HR-negative status (HzR = 1.63; 1.41, 1.89), rMBC (HzR = 1.88; 1.58, 2.23), older age (70 +) (HzR = 1.88; 1.58, 2.24), > 1 distant metastases (HzR 1.39; 1.20, 1.62), and visceral dominant disease (HzR 1.22; 1.05, 1.43). After 1998, HER2-positive disease was associated with better DSS (HzR = 0.72, 95% CI 0.56, 0.93). CONCLUSIONS: Factors associated with the widening survival gap and non-equivalence between dnMBC and rMBC and decreased rMBC incidence warrant further study.

Triple-negative breast cancer in the elderly: Prognosis and treatment.

Our objective is to characterize treatment of triple-negative breast cancer (TNBC) in older patients and measure mortality risk relative to younger women. We conducted a retrospective cohort study analysis of patients presenting with primary TNBC, age 25-93, stage I-III from 1990 to 2014, identified and tracked by our registry (n=771). Clinical characteristics were chart abstracted at diagnosis and follow-up. The Kaplan-Meier method was used to measure disease-specific survival (DSS) by age with Cox regression modeling for relative contribution of patient and clinical characteristics. Of patients, 80% were <65 years (n=612), 13% were 65-74 years (n=100), and 7% were 75 and older (n=59). Older women presented more often with lower stage BC (stage I: 31% age <65, 48% age 65-74, 39% age 75+; P=.014). All three age groups were equally likely to have radiation therapy (77%) but older patients were less often treated with adjuvant chemotherapy (<65=95%, 65-74=76%, 75+=39%; P<.001). Mean follow-up was 7.34 years and did not differ by age. Five-year DSS was equivalent across the three age groups (<65=85%, 65-74=90%, 75+=83%, P=.322). In Cox regression analysis controlling for stage, histologic and nuclear grade, diagnosis year, radiation and chemotherapy treatment, age was not significantly associated with disease-specific mortality. TNBC survival appears equivalent by age despite less aggressive treatment in patients 75 years and older. This may be a result of lower stage at diagnosis and decreased disease virulence resulting in comparative survival despite less treatment.

Therapy-related myelodysplastic syndrome following primary breast cancer.

BACKGROUND: Therapy-related myelodysplastic syndrome (t-MDS) is a serious clinical disease occurring after breast cancer treatment. METHODS: A cohort of 11,684 invasive breast cancer (BC) patients from 1990-2014 were followed for incidence of t-MDS through institutional and the Surveillance, Epidemiology and End Results (SEER) Program registries. t-MDS cases were identified using ICD-O SEER registry codes, pathology and chart reports. Treatment, cytogenetics, and time from BC diagnosis to t-MDS and t-MDS diagnosis to last follow up or death were obtained. Incidence rate ratios were calculated using SEER national incidence rates for comparison. RESULTS: 27 cases of t-MDS post BC treatment were confirmed. 96% of cases were breast cancer stage I-II at diagnosis. All patients had received radiation treatment and 59% received adjuvant chemotherapy. Two patients were alive with no evidence of disease after treatment with stem cell transplantation (age 33 and 46). t-MDS incidence was 30 times the expected population rate among patients <55 years (RR 31.8, 95% CI 15.0, 60.8) with shorter time from t-MDS diagnosis to death (median survival time: <55: 8 months, 55-74: 26 months, 75+: 23 months). CONCLUSION: We found elevated t-MDS risk especially among younger BC patients with stem cell transplantation the only observed curative treatment.

Myelodysplastic syndrome and acute myeloid leukemia following adjuvant chemotherapy with and without granulocyte colony-stimulating factors for breast cancer.

Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. We conducted a retrospective cohort study of women aged ≥66 years with stage I-III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy, and/or G-CSF. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for MDS/AML risk. Among 56,251 breast cancer cases, 1.2 % developed MDS/AML during median follow-up of 3.2 years. 47.1 % of women received radiation and 14.3 % received chemotherapy. Compared to breast cancer cases treated with surgery alone, those treated with chemotherapy (HR = 1.38, 95 %-CI 0.98-1.93) and chemotherapy/radiation (HR = 1.77, 95 %-CI 1.25-2.51) had increased risk of MDS/AML, but not radiation alone (HR = 1.08, 95 % CI 0.86-1.36). Among chemotherapy regimens and G-CSF, MDS/AML risk was differentially associated with anthracycline/cyclophosphamide-containing regimens (HR = 1.86, 95 %-CI 1.33-2.61) and filgrastim (HR = 1.47, 95 %-CI 1.05-2.06), but not pegfilgrastim (HR = 1.10, 95 %-CI 0.73-1.66). We observed increased MDS/AML risk among older breast cancer survivors treated with anthracycline/cyclophosphamide chemotherapy that was enhanced by G-CSF. Although small, this risk warrants consideration when determining adjuvant chemotherapy and neutropenia prophylaxis for breast cancer patients.

Effect of treatment and mammography detection on breast cancer survival over time: 1990-2007.

BACKGROUND: The extent to which improvements over time in breast cancer survival are related to earlier detection by mammography or to more effective treatments is not known. METHODS: At a comprehensive cancer care center, the authors conducted a retrospective cohort study of women ages 50 to 69 years who were diagnosed with invasive breast cancer (stages I through III) and were followed over 3 periods (1990-1994, 1995-1999, and 2000-2007). Data were abstracted from patient charts and included detection method, diagnosis, treatment, and follow-up for vital status in the institutional breast cancer registry (n = 2998). The method of detection was categorized as patient or physician detected or mammography detected. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 5-year disease-specific survival in relation to detection method and treatment factors, and differences in survival were analyzed using the Kaplan-Meier method. RESULTS: Fifty-eight percent of breast cancers were mammography detected, and 42% were patient or physician detected; 56% of tumors were stage I, 31% were stage II, and 13% were stage III. The average length of follow-up was 10.71 years. The combined 5-year disease-specific survival rate was 89% from 1990 to 1994, 94% from 1995 to 1999, and 96% from 2000 to 2007 (P < .001). In an adjusted model, mammography detection (HR, 0.43; 95% CI, 0.27-0.70), hormone therapy (HR, 0.47; 95% CI, 0.30-0.75), and taxane-containing chemotherapy (HR, 0.61; 95% CI, 0.37-0.99) were significantly associated with a decreased risk of disease-specific mortality. CONCLUSIONS: Better breast cancer survival over time was related to mammography detection, hormone therapy, and taxane-containing chemotherapy. Treatment improvements alone are not sufficient to explain the observed survival improvements over time.

Improved prognosis of women aged 75 and older with mammography-detected breast cancer.

PURPOSE: To evaluate the characteristics and outcomes of women aged 75 years and older with mammography-detected breast cancer, an age group not represented in mammography screening effectiveness studies. MATERIALS AND METHODS: We conducted a HIPAA-compliant, prospective cohort study with waiver of informed consent in patients with primary breast cancer, aged 75 years and older, with stage 0-IV disease from 1990 to 2011, identified and tracked with our registry database (n = 1162). Details including stage, treatment, outcomes, and method of detection (by patient, physician, or mammography) were noted from the chart at the time of diagnosis. Kaplan-Meier estimation was used to compare invasive disease-specific survival rates. RESULTS: Among patients with breast cancer aged 75 years and older, mammography detection of cancers increased over time, from 49% to 70% (P < .001). Mammography-detected cases were more often stage I (62%), whereas patient- and physician-detected cases were more likely stage II and III (59%). Over time, from 1990 to 2011, the incidence of stage II cancers decreased by 8%, the incidence of stage III cancers decreased by 8%, and the incidence of stage 0 cancers increased by 15% (P < .001). Patients with mammography-detected invasive breast cancer were more often treated with lumpectomy and radiation and underwent fewer mastectomies and less chemotherapy than patients with cancer detected by patients and physicians (P < .001). Mammography detection was associated with significantly better 5-year disease-specific survival for invasive breast cancer (97% vs 87% for patient- and physician-detected cancer [P < .001], respectively). CONCLUSION: Mammography-detected breast cancer in women 75 years and older was diagnosed at an earlier stage, required less treatment, and had better disease-specific survival than patient- or physician-detected breast cancer. These findings indicate that the same benefits of mammography detection observed in younger women extend to older women.

Age related risk of myelodysplastic syndrome and acute myeloid leukemia among breast cancer survivors.

UNLABELLED: Increased incidence of acute myeloid leukemia (AML) has been identified among breast cancer (BC) survivors but measurement has not included myelodysplastic syndrome (MDS). Our aim is to identify age and stage related MDS/AML incidence post BC diagnosis. We used the 2001-2009 Surveillance, Epidemiology, and end results (SEER) database to identify first primary stage I-III BC patients. Subsequent MDS or AML diagnosis was identified with observed rates compared to expected MDS/AML incidence in the general population. Age adjusted observed/expected rate ratios and 95 % confidence intervals (CI) were calculated. The unadjusted all age and stage MDS/AML incidence rate was .15 % (470/306,691) with a progressively higher rate by age (age 20-49 = .11, age 50-64 = .14, age 65+ =.21, and age 75+ =.18) and stage (stage I = .11, stage II = .18, and stage III = .22). Compared to the general population, BC patients had a 2.75-fold [95 % CI 2.51-3.00] increased relative risk of being diagnosed with MDS/AML. Young age survivors had highest relative risk [age 20-49: relative risk (RR) = 10.60 (95 % CI 8.57-12.93); age 50-64: 5.96 (95 % CI 5.13, 6.88); age 65-74 year-olds: 2.94 (95 % CI 2.45, 3.50); and age ≥75 year-olds: 1.28 (95 % CI 1.03, 1.56)]. Separately MDS relative risk was highest among young women [30.44 (95 % CI = 19.63, 44.62)]. MDS/AML relative risk increased from 1.87 to 5.66 for stage I-III. CONCLUSIONS: Myelodysplastic syndrome and acute myeloid leukemia relative risk is substantially elevated among breast cancer survivors especially those aged 20-49. While the actual number is small, MDS/AML is a serious disease. More research is needed to identify the treatments that put women at risk and find less leukemogenic options, especially for young women.

Adjuvant chemotherapy and differential invasive breast cancer specific survival in elderly women.

OBJECTIVE: To assess adjuvant chemotherapy recommendations, administration and disease-specific survival for invasive breast cancer (BC) among patients 75years and older compared with that of younger women. MATERIALS AND METHODS: A cohort of patients with primary breast cancer, aged 65-94, stages I-III from 1990 to 2010 was identified and tracked by our breast cancer registry (n=2329). Stage, treatment recommendations and outcomes were chart abstracted at diagnosis and follow-up. Associations were tested with logistic regression and the Kaplan-Meier method was used for disease-specific survival (DSS). RESULTS: Seventy-five percent of patients aged 75+ were seen by an oncologist compared with 78% aged 70-74 and 84% aged 65-69. Women aged 75+ seen by an oncologist were more likely age 75-79, stage II/III, hormone receptor negative (HR-) or her-2/neu positive. Of these patients, age, stage and HR status were related to a chemotherapy recommendation. Of 106 patients recommended for chemotherapy, 18 refused (17%) and 24 did not complete treatment due to complications, patient choice, disease progression or death not related to treatment. DSS was equivalent for patients 75 and older with stage I BC compared to 65-74year olds, but significantly worse in stage II and III patients, respectively (stage II 5year DSS 90% vs. 97%, stage III 5year DSS 65% vs. 81%). CONCLUSION: Patients aged 75 and older with invasive breast cancer who were recommended for adjuvant chemotherapy have a high rate of refusal and complications from therapy. Their disease specific mortality disadvantage is restricted to stage II and III patients, a group in need of effective therapy to improve disease survival.

A randomized multiinstitution comparison of the laparoscopic Nissen and Hill repairs.

BACKGROUND: Laparoscopic Hill repair (LHR) and laparoscopic Nissen fundoplication (LNF) are established surgical antireflux procedures but have never been compared in a prospective trial. This trial was designed to compare the effectiveness of LHR against the gold-standard LNF. METHODS: Patients with uncomplicated gastroesophageal reflux from two esophageal centers were randomly assigned and blinded from 2003 to 2007. Preoperative and postoperative evaluation included two quality of life metrics--Quality of Life in Reflux and Dyspepsia, and Dysphagia--as well as endoscopy, video esophogram, manometry, and pH testing. RESULTS: Of 121 patients who consented to the trial, 102 underwent surgery; 46 LNF and 56 LHR were performed, with a mean follow-up of 12 months. Postoperatively, the DeMeester score normalized for both repairs, with no difference between them (LNF 6.8, LHR 11.1, p=0.26). Postoperative medication use was 4%, and the groups were equivalent. Lower esophageal sphincter pressure increased significantly for LNF (14.93 to 24.10, p=0.001) but not for LHR (19.91 to 20.25, p=0.87). Quality of life scores improved significantly for both repairs (LNF 3.77 to 6.65; LHR 3.84 to 6.54, p<0.001), and postoperative results were equivalent (p=0.99). Dysphagia scores preoperative/postoperative were LNF 33.88 to 38.33 and LHR 35.44 to 38.72, and were equivalent postoperatively (p=0.94). Two LNF and two LHR required reoperation for failed repair. CONCLUSIONS: The LHR and the LNF both yield excellent and equivalent results for uncomplicated gastroesophageal reflux at 12 months. Their mechanisms of action may be different.

Impact of mammography detection on the course of breast cancer in women aged 40-49 years.

PURPOSE: To analyze trends in detection method related to breast cancer stage at diagnosis, treatments, and outcomes over time among 40-49-year-old women. MATERIALS AND METHODS: i This study was institutional review board approved, with a waiver of informed consent, and HIPAA compliant. A longitudinal prospective cohort study was conducted of women aged 40-49 years who had primary breast cancer, during 1990-2008, and were identified and tracked by a dedicated registry database (n = 1977). Method of detection--patient detected (PtD), physician detected (PhysD), or mammography detected (MamD)--was chart abstracted. Disease-specific survival and relapse-free survival statistics were calculated by using the Kaplan-Meier method for stage I-IV breast cancer. RESULTS: A significant increase in the percentage of MamD breast cancer over time (28%-58%) and a concurrent decline in patient and physician detected (Pt/PhysD) breast cancer (73%-42%) (Pearson x(2) = 72.72, P < .001) were observed over time from 1990 to 2008, with an overall increase in lower-stage disease detection and a decrease in higher-stage disease. MamD breast cancer patients were more likely to undergo lumpectomy (67% vs 48% of Pt/PhysD breast cancer patients) and less likely to undergo modified radical mastectomy (25% vs 47% of the Pt/PhysD breast cancer patients) (P < .001). Uncorrected for stage, 13% of MamD breast cancer patients underwent surgery and chemotherapy versus 22% of Pt/PhysD breast cancer patients (P < .001), and 31% of MamD breast cancer patients underwent surgery, radiation therapy, and chemotherapy versus 59% of Pt/PhysD breast cancer patients (x(2) = 305.13, P < .001). Analyzing invasive cancers only, 5-year relapse-free survival for MamD breast cancer patients was 92% versus 88% for Pt/PhysD patients (log-rank test, 12.47; P < .001). CONCLUSION: Increased mammography-detected breast cancer over time coincided with lower-stage disease detection resulting in reduced treatment and lower rates of recurrence, adding factors to consider when evaluating the benefits of mammography screening of women aged 40-49 years.

Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990-2005.

BACKGROUND: Our objective was to measure myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) risk associated with radiation and/or chemotherapy breast cancer (BC) treatment. METHODS: Our study cohort was composed of BC patients diagnosed from 1990 to 2005 and followed up for blood disorders, mean length of follow up = 7.17 years, range 2-18 years. 5790 TNM stage 0-III patients treated with surgery alone, radiation and/or chemotherapy were included. Patients without surgery (n = 111), with stem cell transplantation (n = 98), unknown or non-standard chemotherapy regimens (n = 94), lost to follow up (n = 66) or 'cancer status unknown' (n = 67) were excluded. Rates observed at our community based cancer care institution were compared to SEER incidence data for rate ratio (RR) calculations. RESULTS: 17 cases of MDS/AML (10 MDS/7 AML) occurred during the follow up period, crude rate .29% (95% CI = .17, .47), SEER comparison RR = 3.94 (95% CI = 2.34, 6.15). The RR of MDS in patients age < 65 comparing our cohort incidence to SEER incidence data was 10.88 (95% CI = 3.84, 24.03) and the RR of AML in patients age < 65 was 5.32 (95% CI = 1.31, 14.04). No significant increased risk of MDS or AML was observed in women ≥ 65 or the surgery/chemotherapy-only group. A RR of 3.32 (95% CI = 1.42, 6.45) was observed in the surgery/radiation-only group and a RR of 6.32 (95% CI = 3.03, 11.45) in the surgery/radiation/chemotherapy group. 3 out of 10 MDS cases died of disease at an average 3.8 months post diagnosis and five of seven AML cases died at an average 9 months post diagnosis. CONCLUSIONS: An elevated rate of MDS and AML was observed among breast cancer patients < 65, those treated with radiation and those treated with radiation and chemotherapy compared to available population incidence data. Although a small number of patients are affected, leukemia risk associated with treatment and younger age is significant.

Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients.

PURPOSE: Human epidermal growth factor receptor 2 (HER2)/neu, topoisomerase II alpha (TOP2A), and polysomy 17 may predict tumor responsiveness to doxorubicin (DOX) therapy. METHODS: We identified neoadjuvant DOX/cyclophosphamide treated breast cancer patients in our registry from 1997 to 2008 with sufficient tissue for testing (n = 34). Fluorescence in situ hybridization (FISH) testing was done on deparaffinized tissue sections pretreated using vendor's standard protocol modification, and incubated with US Food and Drug Administration approved Abbott Diagnostics Vysis PathVysion™ probe set, including Spectrum-Green-conjugated probe to α-satellite DNA located at the centromere of chromosome 17 (17p11.1-q11.1) and a Spectrum-Orange-conjugated probe to the TOP2A gene. Morphometric analysis was performed using a MetaSystems image analysis system. Manual counting was performed on all samples in which autofluorescence and/or artifact prevented the counting of sufficient numbers of cells. A ratio >2.0 was considered positive for TOP2A amplification. Polysomy 17 (PS17) presence was defined as signals of ≥2.5. Outcomes were pathological complete response (pCR), partial response (PR), and nonresponse (NR). RESULTS: Of 34 patients tested, one was TOP2A amplified (hormone receptor negative/HER2 negative, partial responder). The subset of TOP2A nonamplified, HER2 negative, and PS17 absent (n = 23) patients had treatment response: pCR = 2 (9%), PR = 14 (61%), and NR = 7 (30%). Including the two PS17 present and HER2-positive patients (n = 33), 76% of TOP2A nonamplified patients had pCR or PR. CONCLUSIONS: We observed substantial treatment response in patients lacking three postulated predictors that would be difficult to attribute to cyclophosphamide alone. Patients who are HER2 negative and lack TOP2A amplification and PS17 should not be excluded from receiving DOX-containing regimens.