Risk Of Breast Cancer-related Death Research Articles

Primary tumor removal improves the prognosis in patients with stage IV breast cancer: A population-based study (cohort study).

Adjuvant therapy including chemotherapy, hormonal therapy, and radiotherapy were often used as a common stereotypy for female stage IV breast cancer rather than surgery. This study aimed to define the role of local surgery in metastatic breast cancer. Female metastatic breast cancer patients were identified in the Surveillance, Epidemiology, and End Results (SEER) program data (2010-2013). We compared survival time between patients who received primary tumor removal (PTR) versus those who did not. Multivariate Cox regression models and competitive risk models were built to adjust potential confounders. Of 7669 female stage IV breast cancer patients, 2704 (35.3%) had surgery on their breast tumor and 4965 (64.7%) did not. In the entire cohort, women who underwent PTR had a 45% reduced risk of breast cancer-related death (multi-adjusted hazard ratio [HR], 0.55; 95% CI, 0.50 to 0.60) compared with women who did not undergo PTR (P<0.001). In a cause-specific hazard model (CS model), the multivariable HRs (95% CI) for the association of PTR with breast cancer related-death were 0.54 (0.50-0.60) in the multivariate-adjusted analysis. Similar results were also observed in the sub-distribution hazard function model (SD model) with corresponding multivariate HRs (95%CI) of 0.57 (0.52-0.63). Our study suggested that PTR was associated with improved survival in female stage IV breast cancer patients. The role of PTR in these patients needs to be re-evaluated.

Elevated levels of tumour apolipoprotein D independently predict poor outcome in breast cancer patients.

Apolipoprotein D (ApoD) is a protein that is regulated by androgen and oestrogen, and is a major constituent of breast cysts. Although ApoD has been reported to be a marker of breast cancer, its prognostic importance in invasive breast cancer is unclear. The aim of this study was to investigate the relationship between ApoD protein expression, oestrogen receptor-α (ERα) expression and androgen receptor (AR) expression in predicting breast cancer outcome. ApoD levels were measured by the use of immunohistochemistry and video image analysis on tissue sections from a breast cancer cohort (n=214). We assessed the associations of ApoD expression with disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS). We also assessed the relationship between ApoD expression, AR expression and ERα expression in predicting OS. ApoD expression (>1% ApoD positivity) was found in 72% (154/214) of tissues. High ApoD positivity (≥20.7%, fourth quartile) was an independent predictor of MFS and OS, and conferred a 2.2-fold increased risk of developing metastatic disease and a 2.1-fold increased risk of breast cancer-related death. ApoD positivity was not associated with AR or ERα nuclear positivity. However, patients with (≥1%) ERα-positive cancers with low (<20.7%) ApoD positivity, or those showing high (≥78%) AR positivity and low (<20.7%) ApoD positivity had better OS than other patient groups. ApoD expression could be used to predict breast cancer prognosis independently of ERα and AR expression.

Risk of breast cancer-related death in women with a prior cancer.

The overall risk of developing a second primary cancer is increasing. The purpose of this study was to analyze the survival of patients with breast cancer diagnosed after a prior cancer and identify risk factors of breast cancer death in this population. Using the SEER database, we identified 1,310 woman diagnosed with breast cancer between 2010 and 2015 after a prior cancer as the primary cohort. Clinicopathological characteristics were compared using the Student t-test and chi-square test. Fine and Gray’s regression was used to evaluate the effect of treatments on breast cancer death. After propensity score matching (PSM), 9,845 pairs of patients with breast cancer as the prior or second cancer diagnosed between 2010 and 2011 were included as a second cohort. PSM-adjusted Kaplan-Meier and Cox hazards models were used to evaluate the impact of prior cancer on survival. The results showed that survivors of gynecologic cancers (e.g., ovarian cancer) had a higher risk of developing breast cancer than survivors of gastrointestinal and urinary tract cancers. More patients died of breast cancer than of prior urinary cancer (53.3% vs. 40%, P < 0.05) and melanoma (66.7% vs. 33.3%, P < 0.05). The ratio of breast cancer deaths to prior cancer deaths was significantly higher in patients with diagnoses interval ≥ 3 years than in those with the interval < 3 years (2.67 vs. 0.69, P < 0.001). Breast cancer-specific survival and overall survival rates were significantly lower in women with breast cancer as the second primary cancer than in those with breast cancer as the prior cancer, especially among hormone receptor-positive women. However, breast cancer treatment decreased the risk of breast cancer -specific death (hazard ratio = 0.695, 95% confidence interval: 0.586–0.725, P < 0.001). Breast cancer patients with prior cancers must be carefully considered for clinical trials.

Evaluation of the 8th edition of the American joint committee on cancer’s pathological staging system in prognosis assessment and treatment decision making for stage T1-2N1 breast cancer after mastectomy

PurposeThe 8th edition of the American Joint Committee on Cancer (AJCC) pathological staging system for breast cancer considers biologic factors in addition to the anatomical features included in the previous systems. The purpose of this study was to determine the validity of the 8th AJCC staging system for T1-2N1 breast cancer and to assess the effect of additional chemotherapy and radiotherapy according to the new pathologic stages. MethodsThe cohort included patients from the Surveillance, Epidemiology, and End Results program (2010–2012) who had stage T1-2N1 invasive breast carcinoma and underwent mastectomy. All patients were restaged using the 8th AJCC staging system. The Kaplan–Meier method, Cox proportional hazards regression, and competing risks models were used for data analysis. ResultsWe identified 9908 patients including 3022 (30.5%), 3131 (31.6%), 1940 (19.6%), 1194 (12.1%), and 621 (6.3%) were classified with stage IA, IB, IIA, IIB, and IIIA disease, respectively. The 5-year breast cancer-specific survival (BCSS) was 97.3%, 94.3%, 88.3%, 84.0%, and 71.1% for stage IA, IB, IIA, IIB, and IIIA disease, respectively. Higher pathological stage was associated with a significantly higher risk of breast cancer-related death. Chemotherapy was associated with better BCSS regardless of the pathological stage, but radiotherapy was only associated with better BCSS in stage IIIA disease. ConclusionsThe 8th AJCC pathological staging system provides more refined stratification for T1-2N1 breast cancer patients after mastectomy and may meet the needs of the current trend of individualized decision making for chemotherapy and radiotherapy in this patient subset.

Vitamin D receptor expression in invasive breast tumors and breast cancer survival

BackgroundVitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis.MethodsVDR expression was evaluated in a tissue microarray of 718 invasive breast tumors. Covariation between VDR expression and established prognostic factors for breast cancer was analyzed, as well as associations between VDR expression and breast cancer mortality.ResultsWe found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67. In addition, both intranuclear and cytoplasmic VDR expression were associated with a low risk of breast cancer mortality, hazard ratios 0.56 (95% CI 0.34–0.91) and 0.59 (0.30–1.16) respectively.ConclusionsThis study found that high expression of VDR in invasive breast tumors is associated with favorable prognostic factors and a low risk of breast cancer death. Hence, a high VDR expression is a positive prognostic factor.

Abstract 5695: Use of certain antihistamines among breast cancer patients confers survival benefit

Abstract H1-antihistamines have not been widely studied in relation to cancer therapy, despite being among the most common medications used globally, and having become increasingly sophisticated, cheap and safe. In a nation-wide study of the entire Swedish population using the Drug Prescription Registry, Cancer Registry and Cause of Death Registry- the first of its kind - we investigated the effects of the six major antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) on breast cancer-related (as well as all-cause) mortality. Our study includes 61,627 Swedish women with breast cancer diagnosed between July 1st 2005 and December 31st 2013. 14,711 used at least one of the six major antihistamines. Both peri- and post-diagnostic antihistamine use was analyzed, as well as the use among different subgroups of patients, divided according to age, stage and estrogen receptor status, was analyzed. Here, we show a consistently beneficial effect of desloratadine and ebastine use on breast cancer survival (in the peri-diagnostic analysis, for desloratadine, HR=0.79 [95% CI 0.63-0.99], P=0.044; and for ebastine users, HR=0.57 [95% CI 0.32-1.03], P=0.064; relative to non-users) and a consistently negative effect on breast cancer survival of clemastine use (in the peri-diagnostic analysis, HR=1.24 [95% CI 1.05-1.47], P=0.013; relative to non-users). Loratadine use is associated with better survival in the peri-diagnostic analysis (HR=0.78 [95% CI 0.63-0.97], P=0.022) relative to non-use. No significant effects were seen for cetirizine use or fexofenadine use. Post diagnostic use. A woman with breast cancer using desloratadine will lower her relative risk of breast cancer-related death with 15% after one year's use and 17% after two years' use (both risks relative to a woman of the same age and the same tumor status). Conclusion. Use of desloratadine and ebastine may may significantly improve survival in breast cancer with few side effects. Citation Format: Hakan L. Olsson. Use of certain antihistamines among breast cancer patients confers survival benefit [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5695.

Dosimetric characterisation of anthropomorphic PRESAGE® dosimeter and EBT2 film for partial breast radiotherapy

AbstractPurposeWhole-breast external beam radiotherapy results in significant reduction in the risk for breast cancer-related death, but this may be offset by an increase in deaths from other causes and toxicity to surrounding organs. Partial breast irradiation techniques are approaches that treat only the lumpectomy area rather than the whole breast. Quality assurance in the radiation therapy treatment planning process is essential to ensure accurate dose delivery to the patient. For this purpose, this article compares the results from an anthropomorphic PRESAGE® dosimeter, radiation treatment planning system and from the GAFCHROMIC® EBT2 film.Materials and methodsA breast dosimeter was created and a three-field partial plan was generated in the Pinnacle3 treatment planning system. Dose distribution comparisons were made between Pinnacle3 treatment planning system, GAFCHROMIC® EBT2 film and PRESAGE® dosimeter. Dose–volume histograms (DVHs), gamma maps and line profiles were used to evaluate the comparison.ResultsDVHs of gross tumour volume, clinical tumour volume and planning tumour volume for the PRESAGE® dosimeter and Pinnacle3 treatment planning system shows that both measured and calculated statistics were in agreement, with a value of 97.8% of the prescribed dose. Gamma map comparisons showed that all three distributions passed 95% at the ±3%/±3 mm criteria. Comparisons of isodose line distribution between the PRESAGE® dosimeter, EBT2 film and planning system demonstrated agreement, with an average difference of 1.5%.ConclusionsThis work demonstrated the feasibility of PRESAGE® to function as an anthropomorphic phantom and laid the foundation for research studies in PRESAGE®/optical-computed tomography three-dimensional dosimetry with the most complex anthropomorphic phantoms.

Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death.

Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0.55; P<0.0001). Older patients with higher grade, pT1b, ER-negative breast cancer had increased risk of breast cancer-related death. Adjuvant radiation therapy may provide a CSS benefit in this elderly patient population.

Abstract OT3-07-02: Influence of exercise or educational programs on long-term physical activity by patients after surgery for primary breast cancer: A randomized trial

Abstract [Background] Past studies revealed that a moderate to high level of physical activity after diagnosis of breast cancer reduces both the risk of breast cancer-related death and death from all causes. Furthermore, some randomized studies suggested that exercise programs improve the percentage of patients who complete the chemotherapy and quality of life, and decrease fatigue, and adverse events. The issues to be determined include defining an established uniform exercise program and the efficacy of a long-term exercise program after breast cancer surgery. [Object] To elucidate the efficacy of a long-term exercise program and to verify the safety and feasibility of a uniform exercise program using an ‘existing social resource’ after primary therapy of breast cancer. [Design] A multi-center, randomized trial. [Method] Subjects: The subjects included patients who had completed treatment for primary breast cancer, including surgery and/or adjuvant chemotherapy. Patients with metastatic breast cancer were excluded. Randomization &amp; intervention: The patients were randomly assigned to three groups. The first group followed an exercise program at Curves® that involved 30 minutes of exercise, including aerobics, weight training, and stretching 3 times a week for 4 months. The second group was given life-style guidance at least once that patients participate in a lecture program about recommended exercise at this point and the importance of weight control after diagnosis of breast cancer using a brochure. The third group served as controls that the patients receive a brochure used same one in the second group. The variables included age and weight. Outcome: The primary endpoint is level of physical activity at 1 year after randomization, and the secondary endpoints are the percentage of those completing the exercise program, patient reported outcomes (QOL, cancer or treatment associated symptoms, fatigue, depression, and anxiety), body mass index, bone density, and level of lymphedema. Period of research: The study will last 2 years beginning March 2016. Sample size: We plan to enroll 400 patients to detect 20% difference with 90% power. Additional study: Some biochemical markers in the blood will be evaluated to determine the mechanism of the effect of exercise on the human body. Citation Format: Kawada K, Taira N, Hatono M, Takahashi Y, Miyoshi Y, Nogami T, Iwamoto T, Motoki T, Sien T, Matsuoka J, Doihara H, Ikeda M, Ogasawara Y, Takabatake D, Yoshitomi S, Kiyoto S, Yamamoto S, Mizota Y, Oka K. Influence of exercise or educational programs on long-term physical activity by patients after surgery for primary breast cancer: A randomized trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-07-02.

Crossover effects of estrogen receptor status on breast cancer-specific hazard rates by age and race.

BackgroundPrevious studies found that the risk of breast cancer–related death is greater in estrogen receptor (ER)-negative disease than in ER-positive disease within 5 years of diagnosis, but greater for ER-positive disease than for ER-negative disease more than 5 years after diagnosis. This phenomenon is referred to as ER-positive and -negative crossover. Our aim was to evaluate this crossover by determining the timing of the hazard of breast cancer death by patient, clinical, and tumor factors.MethodsPatients with breast cancer diagnosed between 1990 and 2005 were identified from the Surveillance, Epidemiology, and End Results database. The cohort was evaluated by age at diagnosis, race, tumor ER status, tumor and nodal stage, and tumor grade. Disease-specific (DS) hazard rates were calculated.ResultsOf the 439,444 patients identified, 77.5% had ER-positive disease. Overall, ER-negative to ER-positive DS hazard rates crossed between the years 7 and 8 after diagnosis. Earlier crossover was linked to black or Hispanic race, young age (<40 years), or tumors that were larger, higher grade, or affected the nodes. Young black (<40 years) patients who had a T3/T4 tumor with positive nodes, grade III or undifferentiated, had the earliest crossover, in year 4.ConclusionsThe timing of crossover of death hazard for ER-positive and ER-negative disease varies by clinical and tumor factors. These findings may help guide recommendations regarding the duration of endocrine therapy for patients with ER-positive cancer.

In-Depth Evaluation of the AJCC 2010 Staging System for Luminal-like Breast Cancer-An Analysis from a Free-Standing Cancer Hospital

Purpose: Hormonal receptor (HR) positive breast cancer biologically differs from human epidermal growth factor receptor-2 (HER2) positive disease. The purpose of this study was to re-visit the current AJCC staging system in luminal-like (HR positive and HER2 negative) breast cancer.Materials and Methods: A total of 2051 breast cancer patients treated between 1990 and 2008 were included in this study who met the following criteria: 1) surgery as first treatment; 2) pathology stage I-III; 3) HR positive; and 4) HER2 negative. The T- and N-stage were each re-visited to examine their correlation with 5-year breast cancer-related survival (BCRS).Results: According to the AJCC 2010 staging system, the stage I patients showed a 5-year BCRS of 98.9%; stage IIA: 95.8%; stage IIB: 94.0%; stage IIIA: 90.4%, and stage IIIC: 75.8% (p＜0.001). Re-visiting the T-classification, the 5-year BCRS in T ≤ 0.5 cm N0 patients was same as that of T 1.1-1.5 cm N0 patients (98.4% versus 99.2%); the 5-year BCRS in T1.6-2 cm N1 and N2 patients were no better than those of T ＞2 cm N1 and N2 patients (91.2% and 86.5% versus 94.1% and 88.8%). For the nodal stage, the 5-year BCRS were 91-98.0% for node-negative to 5-node positive patients; the 5-year BCRS were around 80-90% for nodal positivity of 6 to 12, and then dropped below 80% for patients with more than 12 involved nodes.Conclusions: The AJCC 2010 staging system overestimated the risk of breast cancer-related death in early stage luminal-like breast cancer in our hospital. Tumor size 1.5 cm is a crucial point to determine extensive nodal involvement and long-term survivals. Patients with 1-5 positive lymph nodes still had a 5-year BCRS rate exceeding 90%. Given our results, a modification for the current staging system is warranted if other hospitals, especially in Taiwan and Asia, have observed similar outcomes.

HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease

IntroductionStudies have shown that a two-gene ratio (HOXB13:IL17BR) and a five-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) are predictive of clinical outcomes among early-stage breast cancer patients. In an independent population of lymph node-negative breast cancer patients from a community hospital setting, we evaluated the performance of two risk classifiers that have been derived from these gene signatures combined, MGI+HOXB13:IL17BR and the Breast Cancer Index (BCI).MethodsA case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 who did not receive adjuvant chemotherapy. For 191 cases (breast cancer deaths) and 417 matched controls, archived tumor tissues were available and analyzed for expression levels of the seven genes of interest and four normalization genes by RT-PCR. Logistic regression methods were used to estimate the relative risk (RR) and 10-year absolute risk of breast cancer death associated with prespecified risk categories for MGI+HOXB13:IL17BR and BCI.ResultsBoth MGI+HOXB13:IL17BR and BCI classified over half of all ER-positive patients as low risk. The 10-year absolute risks of breast cancer death for ER-positive, tamoxifen-treated patients classified in the low-, intermediate-, and high-risk groups were 3.7% (95% confidence interval (CI) 1.9% to 5.4%), 5.9% (95% CI 3.0% to 8.6%), and 12.9% (95% CI 7.9% to 17.6%) by MGI+HOXB13:IL17BR and 3.5% (95% CI 1.9% to 5.1%), 7.0% (95% CI 3.8% to 10.1%), and 12.9% (95% CI 7.1% to 18.3%) by BCI. Those for ER-positive, tamoxifen-untreated patients were 5.7% (95% CI 4.0% to 7.4%), 13.8% (95% CI 8.4% to 18.9%), and 15.2% (95% CI 9.4% to 20.5%) by MGI+HOXB13:IL17BR and 5.1% (95% CI 3.6% to 6.6%), 18.6% (95% CI 10.8% to 25.7%), and 17.5% (95% CI 11.1% to 23.5%) by BCI. After adjusting for tumor size and grade, the RRs of breast cancer death comparing high- versus low-risk categories of both classifiers remained elevated but were attenuated for tamoxifen-treated and tamoxifen-untreated patients.ConclusionAmong ER-positive, lymph node-negative patients not treated with adjuvant chemotherapy, MGI+HOXB13:IL17BR and BCI were associated with risk of breast cancer death. Both risk classifiers appeared to provide risk information beyond standard prognostic factors.

Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer

IntroductionThe presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether the presence of CTC at the time of diagnosis was associated with recurrence-free survival (RFS) and BRD.MethodsIn a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 602 patients before undergoing surgery for breast cancer. There were 97 patients with a benign tumor, 101 did not meet the inclusion criteria of which there were 48 patients with DCIS, leaving 404 stage I to III patients. Patients were stratified into unfavorable (CTC ≥1) and favorable (CTC = 0) prognostic groups.Results≥1 CTC in 30 ml blood was detected in 15 (15%) benign tumors, in 9 DCIS (19%), in 28 (16%) stage I, 32 (18%) stage II and in 16 (31%) patients with stage III. In stage I to III patients 76 (19%) had ≥1 CTC of whom 16 (21.1%) developed a recurrence. In 328 patients with 0 CTC 38 (11.6%) developed a recurrence. Four-year RFS was 88.4% for favorable CTC and 78.9% for unfavorable CTC (P = 0.038). A total of 25 patients died of breast cancer-related causes and 11 (44%) had ≥1 CTC. BRD was 4.3% for favorable and 14.5% for unfavorable CTC (P = 0.001). In multivariate analysis ≥1 CTC was associated with distant disease-free survival, but not for overall recurrence-free survival. CTC, progesterone receptor and N-stage were independent predictors of BRD in multivariate analysis.ConclusionsPresence of CTC in breast cancer patients before undergoing surgery with curative intent is associated with an increased risk for breast cancer-related death.

Age, hormone receptor status, ethnicity, and adjuvant radiation therapy as predictive factors for cancer-related death in patients age 70 and older with early-stage pT1a,b N0 breast cancer: An NCI-SEER database analysis.

155 Background: Studies have shown that older women are undertreated for breast cancer. Few data are available on 1) cancer-related death in elderly women age 70 and older with pathologic stage T1a, bN0 breast cancer and 2) on the impact of prognostic factors such as increasing age, hormone receptor status (ER), adjuvant radiation therapy (EBRT), chemotherapy, and ethnicity on cancer-related death. Methods: Patient data from SEER database were extracted. Inclusion criteria: females, age 70 and older, pT1a, bN0 invasive breast cancer, ER positive or negative, adjuvant EBRT or no radiation. Cause-specific survival time recorded for all eligible patients. Log-rank test and multivariate Cox regression analysis used for statistical analysis. Hazard ratios (HR) are presented for cancer-related death. Results: ER negative patients had a greater risk of breast cancer death compared to ER positive patients (adjusted HR = 2.34; p &lt; 0.0001). Stage IB patients had a greater risk of breast cancer death compared to stage IA patients (adjusted HR = 1.26; p = 0.09; trend). Patients with no radiation therapy had a greater risk of breast cancer death compared to patients with radiation therapy (adjusted HR = 1.40; p = 0.003). Older age groups had greater risk of breast cancer death compared to patients age 70-74 (referent category) (adjusted HR’s = 1.41, 1.72, and 3.18 for 75-79, 80-84, and 85+ age groups, respectively) (Table). Race had no effect on survival. Conclusions: Patients age 75 and older with T1a, b N0, ER-negative, breast cancer had increased risk of breast cancer-related death. Adjuvant EBRT showed survival benefit in this elderly patient population. Future randomized studies should focus on adjuvant treatments that will improve cancer-related death in this age group. [Table: see text]

Long-Term Outcomes of Invasive Ipsilateral Breast Tumor Recurrences After Lumpectomy in NSABP B-17 and B-24 Randomized Clinical Trials for DCIS

Ipsilateral breast tumor recurrence (IBTR) is the most common failure event after lumpectomy for ductal carcinoma in situ (DCIS). We evaluated invasive IBTR (I-IBTR) and its influence on survival among participants in two National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized trials for DCIS. In the NSABP B-17 trial (accrual period: October 1, 1985, to December 31, 1990), patients with localized DCIS were randomly assigned to the lumpectomy only (LO, n = 403) group or to the lumpectomy followed by radiotherapy (LRT, n = 410) group. In the NSABP B-24 double-blinded, placebo-controlled trial (accrual period: May 9, 1991, to April 13, 1994), all accrued patients were randomly assigned to LRT+ placebo, (n=900) or LRT + tamoxifen (LRT + TAM, n = 899). Endpoints included I-IBTR, DCIS-IBTR, contralateral breast cancers (CBC), overall and breast cancer-specific survival, and survival after I-IBTR. Median follow-up was 207 months for the B-17 trial (N = 813 patients) and 163 months for the B-24 trial (N = 1799 patients). Of 490 IBTR events, 263 (53.7%) were invasive. Radiation reduced I-IBTR by 52% in the LRT group compared with LO (B-17, hazard ratio [HR] of risk of I-IBTR = 0.48, 95% confidence interval [CI] = 0.33 to 0.69, P < .001). LRT + TAM reduced I-IBTR by 32% compared with LRT + placebo (B-24, HR of risk of I-IBTR = 0.68, 95% CI = 0.49 to 0.95, P = .025). The 15-year cumulative incidence of I-IBTR was 19.4% for LO, 8.9% for LRT (B-17), 10.0% for LRT + placebo (B-24), and 8.5% for LRT + TAM. The 15-year cumulative incidence of all contralateral breast cancers was 10.3% for LO, 10.2% for LRT (B-17), 10.8% for LRT + placebo (B-24), and 7.3% for LRT + TAM. I-IBTR was associated with increased mortality risk (HR of death = 1.75, 95% CI = 1.45 to 2.96, P < .001), whereas recurrence of DCIS was not. Twenty-two of 39 deaths after I-IBTR were attributed to breast cancer. Among all patients (with or without I-IBTR), the 15-year cumulative incidence of breast cancer death was 3.1% for LO, 4.7% for LRT (B-17), 2.7% for LRT + placebo (B-24), and 2.3% for LRT + TAM. Although I-IBTR increased the risk for breast cancer-related death, radiation therapy and tamoxifen reduced I-IBTR, and long-term prognosis remained excellent after breast-conserving surgery for DCIS.

Method of detection and breast cancer survival disparities in Hispanic women.

Hispanic women in New Mexico (NM) are more likely than non-Hispanic women to die of breast cancer-related causes. We determined whether survival differences between Hispanic and non-Hispanic women might be attributable to the method of detection, an independent breast cancer prognostic factor in previous studies. White women diagnosed with invasive breast cancer from 1995 through 2004 were identified from NM Surveillance Epidemiology End Results (SEER) files (n = 5,067) and matched to NM Mammography Project records. Method of cancer detection was categorized as "symptomatic" or "screen-detected." The proportion of Hispanic survival disparity accounted for by included variables was assessed using Cox models. In the median follow-up of 87 months, 490 breast cancer deaths occurred. Symptomatic versus screen-detection was classifiable for 3,891 women (76.8%), and was independently related to breast cancer-specific survival [hazard ratio (HR), 1.6; 95% confidence interval (95% CI), 1.3-2.0]. Hispanic women had a 1.5-fold increased risk of breast cancer-related death, relative to non-Hispanic women (95% CI, 1.2-1.8). After adjustment for detection method, the Hispanic HR declined from 1.50 to 1.45 (10%), but after inclusion of other prognostic indicators the Hispanic HR equaled 1.23 (95% CI, 1.01-1.48). Although the Hispanic HR declined 50% after adjustment, the decrease was largely due to adverse tumor prognostic characteristics. Reduction of disparate survival in Hispanic women may rely not only on increased detection of tumors when asymptomatic but on the development of greater understanding of biological factors that predispose to poor prognosis tumors.

The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age

BackgroundThe majority of breast cancer patients are postmenopausal women who are increasingly being offered adjuvant chemotherapy. Since the beneficial effect of chemotherapy in postmenopausal patients predominantly occurs in the first 5 years after diagnosis, a prognostic marker for early events can be of use for adjuvant treatment decision making. The aim of this study was to evaluate the prognostic value of the 70-gene prognosis signature for early events in postmenopausal patients. MethodsFrozen tumor samples from 148 patients aged 55–70 years were selected (T1–2, N0) and classified by the 70-gene prognosis signature (MammaPrint™) into good or poor prognosis. Eighteen percent received hormonal therapy. ResultsBreast cancer-specific survival (BCSS) at 5 years was 99% for the good-prognosis signature versus 80% for the poor-prognosis signature group (P=0.036). The 70-gene prognosis signature was a significant and independent predictor of BCCS during the first 5 years of follow-up with an adjusted hazard ratio of 14.4 (95% confidence interval 1.7–122.2; P=0.01) at 5 years. ConclusionThe 70-gene prognosis signature can accurately select postmenopausal patients at low risk of breast cancer-related death within 5 years of diagnosis and can be of clinical use in selecting postmenopausal women for adjuvant chemotherapy.

Prognostic Utility of HOXB13:IL17BR and Molecular Grade Index for Node-Negative Breast Cancer Patients.

Abstract Background: Four studies have reported that a two-gene ratio (HOXB13:IL17BR) may be prognostic and/or predictive of tamoxifen benefit among early stage breast cancer patients. More recently, a 5-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) was reported to predict clinical outcome. We evaluated the performance of these two gene signatures among an independent population of lymph node-negative breast cancer patients from a community hospital setting.Methods: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985-94 and not treated with adjuvant chemotherapy (Habel, 2006). Archived tumor tissues were available on 169 cases (breast cancer deaths) and 335 matched controls and, using RT-PCR, were analyzed for expression levels of the above 7 cancer-related genes and 4 reference genes. Logistic regression methods were used to estimate the 10-year risk and the relative risk (RR) of breast cancer death associated with pre-specified risk categories based on cross-classification of HOXB13:IL17BR and MGI scores.Results: Approximately 50% of patients were classified as low risk by the HOXB13:IL17BR+MGI risk classifier. At 10 years, the risks of breast cancer death for ER+, tamoxifen-treated patients were 3.9% (95% confidence interval (CI) 2.2% - 5.5%), 5.6% (95% CI 2.6% - 8.5%), and 15.6% (95% CI 8.7% - 21.9%) for those in the low, intermediate and high risk groups, respectively. They were 5.9% (95% CI 4.2% - 7.5%), 15.2% (95% CI 8.3% - 21.5%), and 16.5% (95% CI 10.4% - 22.2%) for ER+ patients not treated with tamoxifen. After adjusting for tumor size and grade, the RRs of breast cancer death associated with high vs. low HOXB13:IL17BR+MGI risk categories were attenuated but remained elevated in both treatment groups; the RR continued to be statistically significant in tamoxifen treated patients only.Conclusion: In this population of lymph-node negative patients not treated with adjuvant chemotherapy, the HOXB13:IL17BR+MGI risk classifier was predictive of risk of breast cancer death and appeared to provide risk information beyond standard prognostic factors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4034.

Physical Activity and Survival After Breast Cancer Diagnosis

Physical activity has been shown to decrease the incidence of breast cancer, but the effect on recurrence or survival after a breast cancer diagnosis is not known. To determine whether physical activity among women with breast cancer decreases their risk of death from breast cancer compared with more sedentary women. Prospective observational study based on responses from 2987 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1984 and 1998 and who were followed up until death or June 2002, whichever came first. Breast cancer mortality risk according to physical activity category (<3, 3-8.9, 9-14.9, 15-23.9, or > or =24 metabolic equivalent task [MET] hours per week). Compared with women who engaged in less than 3 MET-hours per week of physical activity, the adjusted relative risk (RR) of death from breast cancer was 0.80 (95% confidence interval [CI], 0.60-1.06) for 3 to 8.9 MET-hours per week; 0.50 (95% CI, 0.31-0.82) for 9 to 14.9 MET-hours per week; 0.56 (95% CI, 0.38-0.84) for 15 to 23.9 MET-hours per week; and 0.60 (95% CI, 0.40-0.89) for 24 or more MET-hours per week (P for trend = .004). Three MET-hours is equivalent to walking at average pace of 2 to 2.9 mph for 1 hour. The benefit of physical activity was particularly apparent among women with hormone-responsive tumors. The RR of breast cancer death for women with hormone-responsive tumors who engaged in 9 or more MET-hours per week of activity compared with women with hormone-responsive tumors who engaged in less than 9 MET-hours per week was 0.50 (95% CI, 0.34-0.74). Compared with women who engaged in less than 3 MET-hours per week of activity, the absolute unadjusted mortality risk reduction was 6% at 10 years for women who engaged in 9 or more MET-hours per week. Physical activity after a breast cancer diagnosis may reduce the risk of death from this disease. The greatest benefit occurred in women who performed the equivalent of walking 3 to 5 hours per week at an average pace, with little evidence of a correlation between increased benefit and greater energy expenditure. Women with breast cancer who follow US physical activity recommendations may improve their survival.

The Canadian National Breast Screening Study. An appraisal and implications for early detection policy.

The recent reports from the Canadian National Breast Screening Study (CNBSS) address the effectiveness of breast cancer screening for women in the 40-49 age group and the benefit of adding mammography to standard clinical breast examination in women aged 50-59. Overall, the CNBSS results do not show reductions in breast cancer mortality after seven years of follow-up in either age group. The CNBSS is an important study that includes a large number of women, rigorous procedures, and thorough follow-up, but there are several caveats to interpreting these results. The study results reported to date are based on small numbers of end point events. There are questions about the effectiveness of the randomization procedures in creating cohorts that initially were at equal risk of breast cancer-related death. It also has been observed that the quality level of mammographic screens obtained at the beginning of the study were not as high as those obtained later. Future reports from the CNBSS are planned and may provide additional data helpful in interpreting the results.