Breast Cancer-specific Survival Rates Research Articles

Correction: Oestrogen receptor negative early operable primary breast cancer in older women-Biological characteristics and long-term clinical outcome.

[This corrects the article DOI: 10.1371/journal.pone.0188528.].

Threats to Belonging among Breast Cancer Survivors: Consequences for Mental and Physical Health

This review summarizes research linking loneliness and low perceived social support, two threats to belonging, to mental and physical health among breast cancer survivors. We also highlight similarities with research using non-cancer populations. Loneliness and low perceived social support are common complaints among breast cancer survivors. Both loneliness and low perceived social support are linked to higher pain, depression, and fatigue, along with worse cognitive function among breast cancer survivors during survivorship. In addition, survivors perceiving lower social support have lower breast cancer-specific and all-cause survival rates relative to those perceiving more support. Loneliness and a lack of perceived social support threaten the need to belong and thus increase risk for mental and physical health problems among breast cancer survivors. These findings mirror research examining belonging threats and health among people without a history of cancer.

Chronological Improvement in Survival of Patients with Breast Cancer: A Large-Scale, Single-Center Study.

PurposeThis study aimed to chronologically evaluate survival of patients with breast cancer in Korea and investigate the observed changes during the last 20 years. We also sought to determine factors that may influence outcomes and changes in the duration of survival over time.MethodsWe retrospectively analyzed a total of 10,988 patients with breast cancer who were treated at our institution between January 1993 and December 2008. We divided the study period into three periods (P1, 1993–1997; P2, 1998–2002; and P3, 2003–2008). We retrospectively reviewed the collected data from the Asan database, including age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment modalities, type of recurrence, and follow-up period.ResultsAt a median follow-up of 8.2 years, we observed that survival outcomes have improved recently. The 5-year breast cancer-specific survival (BCSS) rate also increased from 82.8% in P1 to 92.6% in P3 (p<0.001). The survival rate in patients with tumors at each stage increased in similar patterns in all patients, and, remarkably, there was a significant survival improvement in patients with stage III breast cancer (P1 vs. P3: 5-year BCSS, 57.4% vs. 80.0%, p<0.001). The time period was a significant prognostic factor in multivariate analysis (P1 vs. P2: hazard ratio [HR], 0.83, p=0.035; P1 vs. P3: HR, 0.75, p=0.015).ConclusionThe study results suggest an improvement in breast cancer survival in Korea, which is consistent with the development of treatments and early detection.

Oestrogen receptor negative early operable primary breast cancer in older women-Biological characteristics and long-term clinical outcome.

BackgroundOlder women are at the greatest risk of breast cancer development and a considerable number present with comorbidities. Although the majority of breast cancers in this age group express oestrogen receptor (ER), which makes endocrine therapy (primary or adjuvant) feasible, given the huge size of the elderly population, there remains a significant number of patients, in absolute term, whose tumours do not express ER and their management is challenging.MethodsOf a consecutive series of 1,758 older (≥70 years) women with early operable primary breast cancer managed in a dedicated service from 1973–2010, 252(14.3%) had ER-negative (histochemical (H) score ≤50) tumours. Their clinical outcome was retrospectively reviewed and tumour samples collected from diagnostic core biopsies were analysed for progesterone receptor (PgR), HER2 and Ki67 using immunohistochemistry.ResultsThe commonest primary treatment was surgery (N = 194, 77%) followed by primary endocrine therapy (14.3%), primary radiotherapy (5.6%) and supportive treatment only (3.1%). Among the patients undergoing surgery, most of them had grade 3 (78.1%) and node-negative disease (62.2%). Some of them (21.1%) received postoperative radiotherapy. At a median follow-up of 37.5 months, 117 patients had died, out of which 48.6% were due to breast cancer. For those who underwent surgery, the regional and local recurrence rates were 2% and 1.1% per annum respectively. For those who received primary endocrine therapy, 38% progressed at 6 months, however all patients who had primary radiotherapy achieved clinical benefit at 6 months. Regardless of treatment given, the 5-year breast cancer specific and overall survival rates were 70% and 50% respectively. Biological analysis based on good quality needle core biopsy specimensfrom181 patients showed that 26.8% (N = 49), 16.9% (N = 31) and 70.7% (N = 70)expressed positivity for PgR, HER2 and Ki67 respectively. No correlation between these biomarkers and breast cancer specific survival was demonstrated.ConclusionOestrogen receptor negative early operable primary breast cancer in older women is associated with poor prognostic features in terms of biology and clinical outcome. Surgery appears to produce the best outcome as a primary treatment, however for those where neither surgery nor chemotherapy is appropriate, primary radiotherapy can be beneficial.

A new molecular-based lymph node staging classification determines the prognosis of breast cancer patients

Background:The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can detect metastasis in a whole lymph node based on cytokeratin 19 mRNA copy number. This cohort study aimed to establish an OSNA-based nodal staging (pN(mol)) classification for breast cancer.Methods:The cohort consisted of 1039 breast cancer patients who underwent sentinel node (SN) biopsy using the OSNA assay. Cutoff value of the SN tumour burden stratifying distant disease-free survival (DDFS) was determined, and predictive factors for DDFS and breast cancer-specific survival (BCSS) were investigated. pN(mol) classification of the SN status was defined as: pN0(mol)(sn), SN negative; pN1mi(mol)(sn), SN positive and tumour burden <cutoff-value; and pN1(mol)(sn), tumour burden ⩾cutoff-value. Median follow-up time; 68.3 months.Results:Cutoff value of the SN tumour burden was 2810 copies per μl. Of the 1039 patients, 798, 95, and 146 had pN0(mol)(sn), pN1mi(mol)(sn), and pN1(mol)(sn) status, respectively. Five-year DDFS and BCSS rates were lower for pN1(mol)(sn) patients than for pN1mi(mol)(sn) patients (87.7% vs 98.8%, P=0.001 and 93.1% vs 98.8%, P=0.044, respectively). Multivariate analyses revealed the pN(mol) classification was most significant predictor for DDFS and BCSS.Conclusions:The molecular-based pN classification determines the prognosis of breast cancer patients and could guide therapeutic decision making.

Evaluation of the clinical benefits of adjuvant capecitabine monotherapy in elderly women with breast cancer: A retrospective study.

Capecitabine is orally administered and may be safely and conveniently used in patients with cancer. The antitumor activity of capecitabine in breast cancer was mostly demonstrated in the salvage therapy setting, whereas the effect of adjuvant capecitabine monotherapy in breast cancer remains unclear. The aim of the present study was to evaluate adjuvant capecitabine monotherapy in elderly women with breast cancer. A total of 251 patients were enrolled and survival was compared between elderly breast cancer patients who received adjuvant capecitabine monotherapy and those who received no chemotherapy. Cancer-specific and disease-free survival curves were compared using log-rank tests and survival curves were calculated using the Kaplan-Meier method. Multivariate analyses were conducted using Cox's proportional hazard regression model. There was no significant difference between the clinicopathological characteristics, including age, tumor size, lymph node status, histological grade and hormone status, between patients in the two groups. The breast cancer-specific survival rate was 89.3% in the capecitabine monotherapy group vs. 81.3% in the no chemotherapy group; the difference was not statistically significant (P=0.128). The disease-free survival rate was 81.7% in the capecitabine monotherapy group vs. 65.3% in the no chemotherapy group. Kaplan-Meier analysis indicated a longer disease-free survival in the capecitabine monotherapy group (P=0.015). On Cox regression analysis, capecitabine monotherapy was found to be associated with the disease-free survival rate (P=0.014, hazard ratio=0.500) but not with the cancer-specific survival rate (P=0.181). The adverse events of capecitabine monotherapy were recorded and there was no chemotherapy interruption due to severe adverse reactions. Therefore, adjuvant capecitabine monotherapy in elderly women with breast cancer is a safe and effective option, as well as a viable alternative for elderly breast cancer patients who refuse standard adjuvant therapy.

Utility of Regular Radiological Follow-up on Early Detection of Contralateral Malignancy and Long-term Outcomes in Metachronous Bilateral Breast Cancer Patients

Objectives We investigated the utility of regular radiological follow-up on the early detection of contralateral breast cancer(CBC) and prognosis in patients with metachronous bilateral breast cancer. Methods Between 1983 and 2010, 49(2.1%) metachronous bilateral breast cancer patients were identified among a total of 2,343 cases of invasive or in situ breast carcinomas. We reviewed the patients' medical records including age, stage, duration between the first and second breast cancer diagnosis, operation method, recurrence, and breast cancer-specific survival. Results The mean ages at the first and second breast cancer diagnosis were 43.8 and 49.2 years, respectively. The mean duration between the first and second breast cancer diagnosis was 68.9 months (range, 7–266 months). Regular radiological follow-up with annual mammography(MMG) with or without ultrasonography was conducted in 28 patients (63.6%, Group 1), and no regular follow-up was performed in 12 patients (27.3%, Group 2). The median follow-up duration was 150 months. In a comparative analysis, Group 1 patients exhibited more stage 0 and stage 1 malignancies (82.1% vs. 25%, P =0.006) as second cancer and the same or an improved stage (71.4% vs. 33.3%, P =0.042) of second cancer compared to Group 2 patients. Breast cancer-specific survival rates between the two groups after the first cancer occurrence were higher in Group 1 patients compared to Group 2 patients, although this did not reach statistical significance. Conclusion Screening for CBC with regular radiological follow-up could result in early detection of CBC, less invasive surgical procedures, and enhanced breast cancer-specific survival outcomes.

The prognostic effect of estrogen receptor status differs for younger versus older breast cancer patients.

To estimate the prognostic impact of estrogen receptor (ER)-status among women with primary invasive breast cancer, according to age at diagnosis. We studied 1910 women with primary invasive breast cancer (stages I-III) who were treated at Women's College Hospital between 1987 and 2000. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, ER-status, treatments received (radiotherapy, chemotherapy and tamoxifen) and dates and causes of death. Patients were followed from the date of diagnosis until the date of death from breast cancer or the date of last follow-up. We used the Kaplan-Meier method to estimate the 15-year actuarial rates of breast cancer-specific survival for women with ER-positive and ER-negative breast cancer, according to age at diagnosis (categories). We used the Cox proportional hazards model to estimate the adjusted hazard ratios for death from breast cancer associated with positive ER-status (compared to negative ER-status), stratified by age at diagnosis. We identified 1347 women with ER-positive breast cancer (70.5%) and 563 women with ER-negative breast cancer (29.5%). Among all 1910 women in the cohort, the actuarial rate of breast cancer-specific survival at 15years was 77% for those with ER-positive breast cancer compared to 70% for those with ER-negative breast cancer (adjusted HR=0.69; 95% CI0.56-0.85; p=0.0006). The prognostic impact of ER-status differed according to age at diagnosis. Among 213 women diagnosed before age 40, breast cancer-specific survival at 15years was worse for those with ER-positive breast cancer than for those with ER-negative breast cancer (55 vs. 61%; adjusted HR=0.90; 95% CI0.57-1.41; p=0.64). In contrast, among 1697 women diagnosed between ages 40 and 75, breast cancer-specific survival at 15years was better for those with ER-positive breast cancer than for those with ER-negative breast cancer (78 vs. 72%; adjusted HR=0.60; 95% CI0.47-0.76; p<0.0001). Positive ER-status is a favourable prognostic factor among women diagnosed with breast cancer at or above age 40, but not among women diagnosed before age 40.

Incorporating Tumor Characteristics to the American Joint Committee on Cancer Breast Cancer Staging System.

The American Joint Committee on Cancer (AJCC) breast cancer staging system provides important prognostic information. The recently published eighth edition incorporates biological markers and recommends the use of a complex "prognostic stage." In this study, we assessed the relationship between stage, breast cancer subtype, grade, and outcome in a large population-based cohort and evaluated a risk score system incorporating tumor characteristic to the AJCC anatomic staging system. Patients diagnosed with primary breast cancer stage I-IV between 2005-2008 were identified in the California Cancer Registry. For patients with stage I-III disease, pathologic stage was recorded. For patients with stage IV disease, clinical stage was utilized. Five-year breast cancer specific survival (BCSS) and overall survival (OS) rates were determined for each potential tumor size-node involvement-metastases (TNM) combination according to breast cancer subtype. A risk score point-based system using grade, estrogen receptor, and human epidermal growth factor receptor 2 (HER2) status was designed to complement the anatomic AJCC staging system. Survival probabilities between groups were compared using log-rank test. Cox proportional hazards models were used. Among 43,938 patients, we observed differences in 5-year BCSS and OS for each TNM combination according to breast cancer subtype. The most favorable outcomes were seen for hormone receptor-positive tumors followed closely by HER2-positive tumors, with the worst outcomes observed for triple negative breast cancer. Our risk score system separated patients into four risk groups within each stage category (all p < .05). Our simple risk score system incorporates biological factors into the AJCC anatomic staging system, providing accurate prognostic information. This study demonstrates that stage, but also breast cancer subtype and grade, define prognosis in a large population of breast cancer patients. It shows that a point-based risk score system that incorporates these biological factors provides refined stratification and information on prognosis, improving the anatomic American Joint Committee on Cancer (AJCC) staging system. In addition, the overall mortality and breast cancer specific mortality rates detailed here provide much-needed information about prognosis in the current era, refining the current AJCC staging.

Clinicopathological characteristics and survival outcomes of male breast cancer according to race: A SEER population-based study.

To investigate the clinicopathological characteristics and survival outcomes of breast cancer in the male population, 8,607 cases of patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database, including white males (n = 7122), black males (n = 1111), and other males (American Indian/AK Native, Asian/Pacific Islander) (n = 374). Black male breast cancer patients were more likely to be in stages II–IV and have more advanced tumors. The rate of lymph node (LN) involvement at diagnosis was higher in black men than in whites and others. The ER- and PR-positive rates were lower in black men than in whites and others. The distant metastasis rate was higher in blacks than in whites and others. Furthermore, the overall survival (OR) rates and breast cancer-specific survival rates were significantly poorer in blacks than in whites and others (χ2 = 29.974, P < 0.001; χ2 = 7.285, P = 0.026, respectively). In a multivariate analysis, the results showed that race could also be a prognostic indicator (P < 0.001). Moreover, significant differences were also observed in OS among 1:1:1 matched white, black, and other groups (P < 0.001). Differences in outcomes may be partially explained by differences in tumor grades, LN status, and ER and PR status between the 3 groups. This study might provide insights into a better understanding of male breast cancer.

Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial

BackgroundThe role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.MethodsThe prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.DiscussionSeveral large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.Trial registrationNCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

Current approach and future perspective for ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) has a good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. In ductal carcinoma in situ without micrometastasis, surgery and postoperative adjuvant therapy significantly improve local control, however it has been reported that the selection of the surgical procedure and adjuvant therapy does not influence breast cancer death. On the other hand, owing to widespread mammography screening, the frequency of early breast cancer detection has increased. In early breast cancer, increased incidence of DCIS is remarkable. However, there is not enough reduction of advanced cancer to match it. Problems with overdiagnosis are now being discussed all over the world. It has been reported that surgery for low-grade ductal carcinoma in situ does not contribute to breast cancer-specific survival. However, it is currently impossible to reliably identify a population that does not progress to invasive cancer even without treatment. Recently, a non-surgery clinical trial for low-risk ductal carcinoma in situ was started. There is a possibility of achieving individualized treatment for ductal carcinoma in situ with less treatment intervention, without compromising the good prognosis obtained with the current treatment approach. This review presents an overview of the current treatment approaches, problems with overdiagnosis and potential future management strategies for ductal carcinoma in situ of the breast.

Which women decide to take tamoxifen?

To identify factors which predict, among estrogen receptor (ER)-positive breast cancer patients, who chooses to take adjuvant tamoxifen. We studied 1347 women with ER-positive breast cancer who were treated at Women's College Hospital between 1987 and 2000. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, ER status, treatments received and dates of local recurrence and of death. We compared women who did and who did not take tamoxifen for a range of factors. We used the Kaplan-Meier method to estimate 15-year local recurrence-free and breast cancer-specific survival rates for women who did and who did not take tamoxifen. Overall, 50.4% of women who had a mastectomy took tamoxifen and 61.0% of women who had a lumpectomy took tamoxifen (p=0.002). Tamoxifen use did not correlate with any of the factors that were predictive of a high risk of death from breast cancer, such as young age, large tumour size and positive lymph node status. Young women (<40years) experienced much higher mortality (41.1%) than older (>60years) women (14.1%, p<0.01), but were much less likely to have taken tamoxifen (35.0 vs. 74.6%, p<0.01). Approximately one-half of women with ER-positive breast cancer who are candidates for tamoxifen did not take tamoxifen. Women with lumpectomy were more likely to take tamoxifen than women with mastectomy. Paradoxically, women at high risk of death from breast cancer (less than 40 at diagnosis and/or lymph node positive) and who are expected to receive the greatest benefit from tamoxifen in terms of mortality reduction were less likely to take it than were low-risk women (older women, lymph node negative). These findings suggest that women consider the reduction in risk from local recurrence to be more important than the reduction in risk of death from breast cancer when they consider taking tamoxifen.

The Use of Hormone Therapy Alone Versus Hormone Therapy and Radiation Therapy for Breast Cancer in Elderly Women: A Population-Based Study

The Cancer and Leukemia Group B (CALGB) 9343 trial randomized elderly women with estrogen receptor-positive, stage 1 breast cancer to receive either hormone therapy (HT) or HT and radiation therapy (HT-RT) after lumpectomy and showed no difference in survival. After this publication, a practice guideline made HT alone a standard treatment option in British Columbia. The subsequent population-based pattern of practice was studied. All women aged 70 to 79years, referred after lumpectomy from 1999 to 2009, with stage 1, estrogen receptor-positive breast cancer were identified. The use of adjuvant HT or HT-RT was evaluated in 2 eras: before (1999-2003) and after (2005-2009) the CALGB publication. The proportion receiving each treatment in these eras was determined. Kaplan-Meier analyses with Cox regression were used for survival endpoints. The Fine and Gray method was used with non-breast cancer death as a competing risk for event-free survival.The Charlson score was used to quantify comorbidity. Adherence was defined as dispensation of 80% of prescribed HT. HT-RT was used in 91% of patients before (n=319) and 89% of patients after (n=403) the CALGB publication (P=.4). In the HT-alone group, the rate of HT adherence was 75% at 1year and 55% at 4years. The 10-year locoregional recurrence-free survival rate was 98% with HT-RT and 90% with HT alone (P=.01), whereas the 10-year breast cancer-specific survival rate was 96% with HT-RT and 95% with HT alone (P=.2). Patients with grade 3 histology or lymphovascular invasion were more likely to have low event-free survival. On multivariate analysis, treatment type did not predict overall survival (P=.3). Our patient outcomes closely matched those of the CALGB trial, suggesting that its results are generalizable to a population of elderly breast cancer patients with typical HT adherence. The CALGB trial results, as well as the resulting practice guideline, did not change the use of adjuvant HT-RT in our population-based cancer program.

Abstract P6-09-46: A comprehensive analysis of GNAS DNA copy number, levels of mRNA and protein expression in primary breast cancer

Abstract Background: Result of recent advances in genetics, guanine nucleotide binding protein, alpha stimulating (GNAS), transducer of signals from G-protein coupled receptors, has been noted that this factor is related with the onset and progression of tumor in various cancers. We aimed to analyze gene amplification, mRNA and protein expression of GNAS and their potential association with clinicopathological factors and prognosis in primary breast cancer. Methods: The cohort of this study included 432 primary invasive breast cancer patients treated with standard care at Kumamoto University Hospital between June 2000 and January 2011. We performed a comprehensive analysis of GNAS at the levels of gene copy number, mRNA and GNAS protein expression analyzed by qPCR, qRT-PCR and immunohistochemistry (IHC), respectively. In the IHC assessment of GNAS protein expression, an H-score&amp;lt;150 was observed in 191 patients (44.2%), who were defined as having a low protein expression level, and an H-score≥150 was observed in 241 patients (55.8%) who were defined as having a high protein expression level. Results: The median age at diagnosis was 60 (range 27-93). Three hundred fifteen (72.9%) of these were postmenopausal women. One hundred forty two patients (32.9%) had axillary lymph node metastasis. The median Ki67 labeling index was 23.6 (range 0.5-97.0). The subtypes were 321 ER+/HER2-, 24 ER+/HER2+, 34 ER-/HER2+ and 53 ER-/HER2-. Three hundred twenty one patients (75.9%) were treated with endocrine therapy and 146 patients (34.6%) chemotherapy. Most notably, a low levels of GNAS protein expression was observed in 191(44.2%) patients, and was positivity associated with Ki67 (P=0.028). Furthermore, univariate and multivariate analysis revealed that low GNAS protein expression was significantly related with poor relapse-free survival rate (Log-rank test; P=0.0013, OR:0.40, 05%CI:0.22-0.70) and breast cancer specific survival rate (Log-rank-test; P=0.041, OR:0.43, 95%CI:0.19-0.97). GNAS amplification and mRNA expression were not correlated with prognoses. Conclusion: Contrary to expectations, GNAS expression was positively related with favorable tumor characteristics. Expression levels of GNAS protein may be an independent prognostic factor for primary breast cancer. Citation Format: Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Goto-Yamaguchi L, Fujiki Y, Sueta A, Takeshita T, Iwase H. A comprehensive analysis of GNAS DNA copy number, levels of mRNA and protein expression in primary breast cancer [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 P6-09-46.

Effect of Age on Breast Cancer Patient Prognoses: A Population-Based Study Using the SEER 18 Database.

BackgroundAge is an important risk factor for breast cancer, but data regarding whether patient age at diagnosis is related to breast cancer survival are conflicting. This population-based study evaluated the effect of age on breast cancer prognosis and identified outcome-related factors.Patients and MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled female primary non-metastatic cases. Patients were subdivided into seven groups, and analyses of the associations between age and overall survival (OS) and breast cancer-specific survival (BCSS) were carried out using the Kaplan-Meier method and Cox regression model, respectively. We also assessed differences in survival among three specific age groups, using the ages of 30 and 50 years as cut-offs. Stratified analyses regarding race, histology, grade, stage and hormone receptor status were also carried out.ResultsA total of 133,057 female patients diagnosed with breast cancer from 2004 to 2008 were included in the current study (6.4% <40 years), Women aged 40 to 49 years and 60 to 69 years exhibited significantly better OS and BCSS, respectively (log-rank, p<0.001), than their counterparts in other groups. Middle-aged women exhibited distinctly better OS (log-rank, p<0.001) and BCSS (log-rank, p<0.001) than their counterparts in the other two age groups. Following adjustments for potential confounding factors, middle-age at breast cancer diagnosis was shown to be an independent predictor of favourable outcomes in terms of OS, but not BCSS (for OS, HR, 0.92; 95%CI, 0.87–0.98; p = 0.007; for BCSS, HR, 0.94; 95%CI, 0.80–1.01; p = 0.075, using the young group as reference). Stratified analysis showed that middle-age was significantly associated with increased survival, except among patients with stage III disease, and that elderly women faced worse prognoses than younger patients.ConclusionOur results indicate that younger breast cancer patients exhibit more aggressive disease than older patients. Middle-aged patients exhibit better OS and BCSS than young and elderly patients but exhibit BCSS rates similar to those of young patients after adjustments for confounders. Stratified analysis demonstrated that middle-aged patients exhibited better survival than young patients, with the exception of patients with stage III disease. An age of 60 years or more was a significant independent predictor of a poor prognosis.

Ten-year survival in women with primary stage IV breast cancer

To evaluate breast cancer-specific survival at 10years in patients who present with primary stage IV breast cancer, and to determine whether survival varies with age of diagnosis. We retrieved the records of 25,323 women diagnosed with primary stage IV breast cancer in the surveillance, epidemiology, and end results 18 registries database from 1990 to 2012. For each case, we extracted information on age at diagnosis, tumour size, nodal status, oestrogen receptor status, progesterone receptor status, ethnicity, cause of death and date of death. The Cox proportional hazards model was used to estimate the unadjusted and adjusted hazard ratio (HR) of death due to stage IV breast cancer, according to age group. Among 25,323 women with stage IV breast cancer, 2542 (10.0%) were diagnosed at age 40 or below, 5562 (22.0%) were diagnosed between ages 41 and 50 and 17,219 (68.0%) were diagnosed between ages 51 and 70. After a mean follow-up of 2.2years, 16,387 (64.7%) women died of breast cancer (median survival 2.3years). The ten-year actuarial breast cancer-specific survival rate was 15.7% for women ages 40 and below, 14.9% for women ages 41-50 and 11.7% for women ages 51 to 70 (p<0.0001). In an adjusted analysis, the risk of death from breast cancer at 10years was significantly lower for women ages 40 and below (HR 0.78; 95% CI 0.74-0.82; p<0.0001) and for women ages 41-50 (HR 0.82; 95% CI 0.79-0.85; p<0.0001), compared to women ages 51-70. Approximately 13% of women with primary stage IV breast cancer survive 10years after diagnosis. Women diagnosed with stage IV breast cancer before age 50 have better survival at 10years compared to older women.

Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and ER-Status: Stimulation of Estrogen Signaling Coupled With Breast Conserving Surgery.

: BackgroundResults of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures.ObjectiveSince the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking.MethodPublished long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients’ age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality.ResultsDiagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ER-positive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumor-growth.ConclusionEstradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer.

Prognostic Significance of Progesterone Receptor Expression in Estrogen-Receptor Positive, HER2-Negative, Node-Negative Invasive Breast Cancer With a Low Ki-67 Labeling Index

IntroductionWe showed the clinical implications of the Ki-67 labeling index (LI) in hormone receptor (HR)-positive, HER2-negative (HER2−) breast cancer patients with lower risk (luminal A [LA]-like) and higher risk (luminal B [LB]-like) subtypes. Patients and MethodsThree hundred sixty-nine patients with HR+, HER2− cancers were eligible and we dichotomized these patients into LA-like and LB-like according to Ki-67 LI (14% cutoff) and analyzed prognostic significance of progesterone receptor (PR) expression. ResultsOf 205 LA-like and 163 LB-like subtypes, PR was positive in 149 (73%) and 103 (63%). PR expression was a prognostic factor in the LA-like subtype but not in the LB-like subtype. In LA/PR+, LA/PR−, and LB-like subtypes, the 12-year disease-free survival (DFS) rates were 94.8%, 81.6%, and 79.7% (P = .03), and breast cancer-specific survival (BCSS) rates were 98.4%, 97.4%, and 92.0%, respectively (P = .05). Late recurrence occurred in LA/PR− subtype, and differences in prognosis between LA/PR+ and LA/PR− subtypes emerged >5 years after surgery. Twelve-year DFS rates of the LA/PR− subtype were almost equal to those of the LB-like subtype, whereas 12-year BCSS of the LA/PR− subtype was superior to that of the LB-like subtype. In multivariate analysis, PR expression and tumor size were significant or nearly significant prognostic factors. ConclusionPR expression and tumor size were independent prognostic factors in the LA-like subtype, and the LA/PR− subtype had the higher risk of recurrence, especially late recurrence, than the LA/PR+ subtype. In LA-like breast cancers, stratification of prognosis according to PR expression and tumor size is important.

Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study.

BackgroundA high neutrophil-to-lymphocyte ratio (NLR) may be related to increased mortality in patients with lung, colorectal, stomach, liver, and pancreatic cancer. To date, the utility of NLR to predict the response to neoadjuvant chemotherapy (NAC) has not been studied. The aim of our study was to determine whether the NLR is a predictor of response to NAC and to investigate the prognostic impact of the NLR on relapse-free survival (RFS) and breast cancer-specific survival (BCSS) in patients with breast cancer who received NAC.MethodsWe retrospectively studied patients who received NAC and subsequent surgical therapy for stage II–III invasive breast carcinoma at Sun Yat-sen Memorial Hospital between 2001 and 2010. The correlation of NLR with the pathological complete response (pCR) rate of invasive breast cancer to NAC was analyzed. Survival analysis was used to evaluate the predictive value of NLR.ResultsA total of 215 patients were eligible for analysis. The pCR rate in patients with lower pretreatment NLR (NLR < 2.06) was higher than those with higher NLR (NLR ≥ 2.06) (24.5 % vs.14.3 %, p < 0.05). Those patients with higher pretreatment NLR (NLR ≥ 2.1) had more advanced stages of cancer and higher disease-specific mortality. Through a multivariate analysis including all known predictive clinicopathologic factors, NLR ≥ 2.1 was a significant independent parameter affecting RFS (HR: 1.57, 95 % CI: 1.05-3.57, p < 0.05) and BCSS (HR: 2.21, 95 % CI: 1.01-4.39, p < 0.05). Patients with higher NLR (NLR ≥ 2.1) before treatment showed significantly lower relapse-free survival rate and breast cancer-specific survival rate than those with lower NLR (NLR <2.1) (log-rank p = 0.0242 and 0.186, respectively).ConclusionsPretreatment NLR < 2.06 is associated with pCR rate, suggesting that NLR may be an important factor predicting the response to NAC in breast cancer patients. NLR is an independent predictor of RFS and BCSS in breast cancer patients with NLR ≥ 2.1 who receive NAC. We suggest prospective studies to evaluate NLR as a simple prognostic test for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2352-8) contains supplementary material, which is available to authorized users.