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).

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.

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.

Examination of a paradox: recurrent metastatic breast cancer incidence decline without improved distant disease survival: 1990-2011.

PURPOSE: Distant relapse metastatic breast cancer (rMBC) incidence and survival are vital measures of breast cancer diagnosis and treatment progress over time. METHODS: We conducted a retrospective cohort study of stage I-III invasive breast cancer, 1990-2011, follow-up through 2016 [N = 8292, rMBC = 964 (12%)] at a community-based institution. Patient and tumor characteristics (treatment, distant recurrence, vital status) from BC registry data were evaluated. Survival analysis and Cox proportional hazards (HzR) with 95% confidence intervals (95% CI) were calculated using distant recurrence and distant disease-specific survival (DDSS) endpoints. RESULTS: Both 5- and 10-year distant relapse (rMBC) declined over time from 1990-1998 to 2005-2011 [11% to 5%, 16% to 8% (p < 0.001)]. Proportionately, HER2 + BC distant relapse decreased 9% and triple negative (HR-/HER2-) increased 8% (p = 0.011). In the Cox model, lower stage [stage I: HzR = 0.08 (0.07, 0.10), stage II: 0.29 (0.25, 0.33)], more recent diagnosis years [1999-2004: HzR = 0.60 (0.51, 0.70), 2005-2011: HzR = 0.44 (0.38, 0.52)], HR+ [HzR = 0.62 (0.53, 0.72)], and age 40+ [HzR = 0.81 (0.67, 0.98)] had decreased rMBC risk. Compared to HR+/HER2- BC, triple-negative BC had increased rMBC risk [HzR = 2.02 (1.61, 2.53)] but HER2+ subtypes did not. HR-, age 70+, > 1, or visceral metastases and stage III disease were associated with worse DDSS. DDSS did not improve over time. CONCLUSION: rMBC incidence declined over time with decreased HER2-positive distant recurrence, a shift to more triple-negative BC and consistently poor distant disease survival.

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.

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.

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.

Breast cancer detection method among 20- to 49-year-old patients at a community based cancer center: 1990-2008.

Our research goal is to report on method of breast cancer detection among young women from a prospective cohort study of primary breast cancer patients, aged 20-49 years, 1990-2008 (n = 2579). Clinical presentation characteristics including race, TNM stage, first degree relative family history, histologic type and method of detection by patient (PtD), physician (PhysD), or mammography (MamD) were chart abstracted. Forward conditional stepwise regression was used to for association with detection method and Kaplan-Meier for relapse free survival (RFS) analysis. Among 20- to 39-year olds (n = 602) no change in detection method occurred over time with 12% MamD, 7% PhysD, and 81% PtD. Among 40- to 49-year olds, MamD BC increased over time (28% to 58%) and PtD BC decreased (63-36%) (Pearson X(2) = 72.72, p < .001). Among 20-39/40- to 49-year old MamD cases 31%/32% were stage 0 versus 2%/6% of the PhysD/PtD cases. In two separate conditional logistic regression models, older age at diagnosis and first degree relative BC history were associated with MamD BC for 20- to 39- and 40- to 49-year olds. Five-year MamD BC RFS was superior for both age groups (20-39: 94%, 40-49: 94%) compared to PtD BC rates (20-39: 80%, p = .016; 40-49: 88%, p < .001). For PtD BC 20- to 39-year olds had worse RFS (5 year 80%, 10 year 75%) than 40- to 49-year olds (5 year 88%, 10 year 82%) (p = .002) but RFS was equivalent for MamD cases by age. The majority of breast cancers among women 20-49 years were patient detected and mammography detection occurred rarely among youngest women. Lower stage and superior survival among MamD patients support mammography for detecting disease in high risk women aged 30-39 years and 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.

Neoadjuvant chemotherapy of breast cancer: tumor markers as predictors of pathologic response, recurrence, and survival.

This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR-) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR- patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR- patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy, but significantly better overall outcome. For both HR- and HR+, addition of NAT for HER2+ tumors results in both a superior response and outcome.

Impact and outcomes of routine microstaging of sentinel lymph nodes in breast cancer: significance of the pN0(i+) and pN1mi categories.

BACKGROUND: In 2003, the American Joint Committee on Cancer (AJCC) initiated the 6th edition staging criteria, including pN0(i+) and pN1mi categories for breast cancer. However, the clinical significance of these categories is debated in the literature. METHODS: A prospective registry was used to identify patients staged with sentinel lymph node (SLN) biopsy. SLN evaluation included routine serial sectioning and immunohistochemical stains. SLN biopsies performed before January 2003 were restaged according to the AJCC's 6th edition criteria. RESULTS: Of 954 SLN biopsies identified, on review, 491 N0i-, 86 N0i+, 73 N1mi, 146 N1a, 29 N2a, and 11 N3a patients were available for analysis with a median follow-up of 45.4 months. Significant prognostic and therapeutic differences existed between the groups. Differences in overall survival (OS) and recurrence-free survival (RFS) were only noted when the size of the metastases reached the N1a level. There were no statistically significant differences in OS or RFS between N0(i-) and N0(i+) or N1mi disease. Cases that were N0(i+) or N1mi were more likely to have other poor prognostic factors and to receive more aggressive therapy. CONCLUSION: SLN biopsy allows a more sensitive evaluation of lymph nodes for metastatic cells. This has led to the increased identification of very small axillary metastases. While the new microstaging categories are not yet clearly associated with a significantly decreased OS or DFS in this series, they are associated with other poor prognostic factors and more local/regional and systemic therapy. Further analysis of the microstaging categories is needed.

T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy.

Adjuvant treatment of T1N0 breast cancer (BC) has evolved in recent years with chemotherapy options dependent on tumor size and cellular characteristics. Our goal is to describe the difference in outcome between T1N0 triple negative (TriNeg) and estrogen/progesterone receptor positive/her2/neu-negative BC. From our institute's registry, we identified primary BC patients diagnosed from 1998 to 2005, estrogen/progesterone receptor negative (ER-/PR-)/her-2/neu negative (her2-) (TriNeg = 110) and ER+/PR+/her2- (HR+/her2- = 919). Clinical diagnosis and treatment variables were chart abstracted. Vital and disease status were updated annually. Pearson chi-squared tests were used for bivariate analysis. Hazard ratios were calculated using the Cox proportional hazards model. Average patient age was 59 years, range 23-93 years and average length of follow-up was 4.22 years. T-stage distribution for HR+/her2- patients was 9% T1a (>0.1, < or = 0.5 cm), 34% T1b (>0.5 cm, < or = 1 cm), 57% T1c (>1 cm, < or = 2 cm) and for TriNeg, 6% T1a, 21% T1b, and 73% T1c. Sixty-five per cent of T1b and 73% T1c TriNeg patients received chemotherapy versus 7% of T1b and 32% of T1c HR+/her2- patients with TriNeg patients more likely to receive doxorubicin/cyclophosphamide/paclitaxel combined therapy. Recurrence rates were the following, T1b: 8.7%, TriNeg (2/23) versus 0%, HR+/her2- (0/315) and T1c: 8.8%, TriNeg (7/80) versus 2.1%, HR+/her2- (11/523). Five year relapse-free survival was 98% in the HR+/her2- group and 89% in the TriNeg group (log rank test = 27.77, p < 0.001). The hazard ratio for recurrence in the TriNeg group was 6.57 (95% CI = 2.34, 18.49) adjusted for age, tumor size, and adjuvant chemotherapy. Triple negative T1N0 patients have greater recurrence risk in spite of more aggressive therapy by both number treated and adjuvant chemotherapy type even in a low-risk category. New treatment modalities specific for triple negative disease are urgently needed.

Increase in mammography detected breast cancer over time at a community based regional cancer center: a longitudinal cohort study 1990-2005.

BACKGROUND: Coincident with the advent of mammography screening, breast carcinoma in situ has increased in the US population. METHODS: We conducted a prospective cohort study of all women presenting with primary breast cancer, aged 21-94, and biopsy confirmed Stage 0-IV from 1990-2005 identified and tracked by our registry. Clinical presentation characteristics including age, race, TNM stage, family and pregnancy history, histologic type and method of detection by patient (PtD), physician (PhysD) or mammography (MgD) were chart abstracted at time of diagnosis. Cases with unknown or other method of detection (n = 84), or unusual cell types (n = 26) were removed (n = 6074). RESULTS: From 1990 to 1998 the percentage of PtD and MgD cases was roughly equivalent. In 1999 the percentage of MgD cases increased to 56% and PtD dropped to 37%, a significant 20% differential, constant to 2005 (Pearson chi square = 120.99, p < .001). Overall, percent TNM stage 0 (breast carcinoma in situ) cases increased after 1990, percent stage I and III cases declined, and stage II and IV cases remained constant (Pearson chi square = 218.36, p < .001). Increase in MgD over time differed by age group with an 8.5% increase among women age 40-49 and 12% increase among women age 50-95. Women age 21-39 rarely had MgD BC. In forward stepwise logistic regression modeling, significant predictors of MgD BC by order of entry were TNM stage, age at diagnosis, diagnosis year, and race (chi square = 1867.56, p < .001). CONCLUSION: In our cohort the relative proportion of mammography detected breast cancer increased over time with a higher increase among women age 50+ and an increase of breast carcinoma in situ exclusively among MgD cases. The increase among women currently targeted by mammography screening programs (age > or = 50) combined with an increase of breast carcinoma in situ most often detected by mammography screening indicates a possible incidence shift to lower stage breast cancer as a result of mammographic detection.

Metaplastic breast cancer: clinical significance.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare poorly differentiated breast cancer characterized by coexistence of ductal carcinoma with areas of matrix producing, spindle-cell, sarcomatous, or squamous differentiation; ER/PR/HER2 negativity; and a reputation for poor outcome. METHODS: The Swedish Cancer Institute prospective breast cancer database (> 6500 patients; 1990-2005) has 24 MBC cases that were compared with typical breast cancer cases matched for age, date of diagnosis, stage, and ER/PR/HER2 status. RESULTS: The mean metaplastic primary tumor diameter was 2.5 cm. The histological/nuclear grade was high in 21 of 24 cases. No patient had distant metastasis. ER and/or PR receptor status was negative in all cases. HER2 was negative in 10 of 11 cases tested. EGFR (HER1) was positive in 7 of 7 cases tested. All patients had sentinel and/or axillary lymph node dissection and surgical resection; 18 received chemotherapy and 22 had radiation therapy. Four patients had distant recurrences 5 to 88 months from diagnosis. Five-year survival was 83% (95% confidence interval, 66-100%). Comparison with matched typical breast cancer cases revealed no major significant difference in multidisciplinary treatment patterns, recurrence, or survival. CONCLUSION: MBC is associated with poor prognostic indicators, but outcomes comparable with matched typical breast cancer cases can be achieved with routine aggressive multidisciplinary care. Increased, expression of EGFR (HER1) provides an opportunity for targeted tumor therapy.

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.

Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma.

OBJECTIVE: To evaluate the efficacy of high dose rate vaginal brachytherapy in the treatment of International Federation of Gynecology and Obstetrics stage IB, IC, and II endometrial carcinoma after surgical staging and complete lymphadenectomy. METHODS: All patients with stage IB, IC, or II adenocarcinoma or adenosquamous carcinoma of the endometrium who received postoperative high dose rate vaginal brachytherapy at our institution between June 1, 1989, and June 1, 1999, were eligible. High dose rate vaginal brachytherapy was delivered in three fractions of 700 cGy. Retrospective chart review was performed. Kaplan-Meier estimates were calculated for disease-free and overall survival. RESULTS: One hundred sixty-four women were identified. Fifty-six percent had stage IB disease, 30% had stage IC disease, and 14% had stage II disease. Approximately one third of patients had high-grade lesions and nearly 40% had deep myometrial invasion. Median follow-up was 65 months (range 6-142 months). To date, 14 patients have had recurrence; 2 at the vaginal apex, 9 at distant sites, 1 at the pelvic sidewall, 1 simultaneously in the pelvis and at a distant site, and 1 at an unknown site. Both patients with vaginal apex recurrences had salvage therapy and are now free of disease. The overall 5-year survival and disease-free survival rates were 87% and 90%, respectively. There were no Radiation Therapy Oncology Group grade 3 or 4 toxicities. High dose rate vaginal brachytherapy was approximately $1,000 less expensive than external-beam whole-pelvic radiation. CONCLUSIONS: Adjuvant high dose rate vaginal brachytherapy in thoroughly staged patients with intermediate-risk endometrial carcinoma provides excellent overall and disease-free survival with less toxicity and at less cost compared with whole-pelvic radiation.