5-year Breast Cancer-specific Survival Research Articles

Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer-specific survival

Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer-specific survival (BCSS) in older women. Cancer registration data for 2002-2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)-positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation. Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER-positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5-year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co-morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival. BCSS in older women with ER-positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit.

Decreased survival in patients with carcinoma of axillary tail versus upper outer quadrant breast cancers: a SEER population-based study

BackgroundCarcinoma of the axillary tail of Spence (CATS) is a poorly studied type of breast cancer. The clinicopathological characteristics and prognostic features of CATS are unclear.MethodsUsing the Surveillance, Epidemiology, and End Results database, we identified 149,026 patients diagnosed with upper outer quadrant breast cancer (UOBC) (n=146,343) or CATS (n=2,683). The median follow-up was 88 months. The primary and secondary outcomes were breast cancer-specific survival (BCSS) and overall survival. The survival outcomes of UOBC and CATS were compared using competing risks analysis, log-rank test, Cox proportional hazards regression model, and propensity score matching method. Multivariate logistic regression was utilized to present the relationship between CATS and lymph node (LN) metastasis.ResultsCATS presented a higher grade, higher negative hormone receptor rate, and more positive nodal metastasis. The 10-year BCSS rate was worse for CATS than for UOBC (85.1% vs 87.3%, P=0.001). The multivariate Cox analysis showed a higher hazard ratio (HR) for CATS over UOBC (BCSS: HR =1.20, P=0.001; overall survival: HR =1.11, P=0.019). The difference in the BCSS was also observed in a 1:1 matched cohort (BCSS P=0.019). A subgroup analysis revealed the inferior outcomes of CATS in the metastatic LN subgroup and the hormone receptor-negative subgroup. The multivariate logistic regression indicated that CATS is an independent contributing factor to LN metastasis.ConclusionCATS had distinct clinicopathological characteristics and was more likely associated with LN metastasis. Compared to UOBC, CATS had adverse impacts on BCSS.

Risk of recurrence and death in patients with breast cancer after delayed deep inferior epigastric perforator flap reconstruction.

BackgroundPostmastectomy reconstruction using a deep inferior epigastric perforator (DIEP) flap is increasingly being performed in patients with breast cancer. The procedure induces extensive tissue trauma, and it has been hypothesized that the release of growth factors, angiogenic agonists and immunomodulating factors may reactivate dormant micrometastasis. The aim of the present study was to estimate the risk of breast cancer recurrence in patients undergoing DIEP flap reconstruction compared with that in patients treated with mastectomy alone.MethodsEach patient who underwent delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013, was compared with up to four controls with breast cancer who did not receive a DIEP flap. The control patients were selected using incidence density matching with respect to age, tumour and nodal status, neoadjuvant therapy and year of mastectomy. The primary endpoint was breast cancer‐specific survival. Survival analysis was carried out using Kaplan–Meier survival estimates and Cox proportional hazard regression analysis.ResultsThe analysis included 250 patients who had 254 DIEP flap reconstructions and 729 control patients. Median follow‐up was 89 and 75 months respectively (P = 0·053). Breast cancer recurrence developed in 50 patients (19·7 per cent) in the DIEP group and 174 (23·9 per cent) in the control group (P = 0·171). The 5‐year breast cancer‐specific survival rate was 92·0 per cent for patients with a DIEP flap and 87·9 per cent in controls (P = 0·032). Corresponding values for 5‐year overall survival were 91·6 and 84·7 per cent (P < 0·001). After adjustment for tumour and patient characteristics and treatment, patients without DIEP flap reconstruction had significantly lower overall but not breast cancer‐specific survival.ConclusionThe present findings do not support the hypothesis that patients with breast cancer undergoing DIEP flap reconstruction have a higher rate of breast cancer recurrence than those who have mastectomy alone.

The characteristics, management and outcomes of older women with breast cancer in New Zealand

The aim of this study was to understand the characteristics of older women with breast cancer and to describe the current patterns of treatment and outcomes. The study included data from the combined Auckland and Waikato breast cancer registers, which hold information for 12, 372 women diagnosed with stage I–IV breast cancer between June 2000 and May 2013. Of these women, 2671 (21.6%) were over 70 years of age. Patient characteristics, treatment type and survival were compared across four-year age groups (70–74, 75–79, 80–84, 85+) and hormone receptor status. Of the women aged over 70 years, 2485 (93.0%) had stage I–III disease. Increasing age was significantly associated with decreasing use of surgery, adjuvant radiotherapy, endocrine therapy and chemotherapy, even after adjustment for stage and level of co-morbidity. Nine hundred and one women (33.7%) had co-morbidities at the time of diagnosis. The 5-year breast cancer-specific survival rate for women aged 70–74 and that for women aged 75–79 were similar, but was worse in women aged over 80. Generally, older women are treated as per guidelines, although chemotherapy may be under-used. However, age is a significant factor influencing whether women are treated or not.

Molecular Characterization and Mortality From Breast Cancer in Men.

Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor-positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer-specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

Abstract P1-06-03: Breast cancer-specific survival (BCSS) in SEER patients with 21-gene Recurrence Score® (RS) results &amp;lt;11 classified as prognostic stage IA by new 8th edition AJCC staging manual

Abstract Introduction: The 8th edition of the AJCC Staging Manual added molecular features for the first time and now includes ER, PR, HER2, and the 21-gene assay for prognostic staging. We obtained real-world evidence of BCSS by age, tumor size, and grade in a population-based SEER analysis of N0, HR+, HER2-negative breast cancer and RS &amp;lt;11 (tumor size up to 5 cm) to obtain more detailed information on clinically “unfavorable” subgroups. Methods: RS results were provided to SEER registries as mandated by their methods for linkage (Petkov npj Breast Cancer 2016). Patients (pts) with RS &amp;lt;11 and size up to 5 cm were eligible if N0, HR+, HER2-negative, had no prior malignancy, and were diagnosed between Jan 2004 and Dec 2012 (SEER survival updated through 2013). 5-year BCSS was estimated using actuarial methods. Results: 9,304 pts had RS &amp;lt;11 (19% of those meeting all other eligibility), with median follow-up of 40 months. Median age was 59 y, with 22% &amp;lt;50 y and 16% ≥70 y. Tumor size was &amp;gt;2 cm in 21% of pts. Tumor grade was moderate in 54% and poor in 8% of pts. Overall, 5-year BCSS for pts with RS &amp;lt;11 was 99.6% (95% CI 99.4%, 99.7%), with reported chemotherapy (CT) use in 3.3% of pts. In contrast, BCSS for pts with RS &amp;gt;25 and RS ≥31 was 3.5% and 4.7%, respectively, with frequent CT use. 5-year BCSS for important clinicopathologic subgroups show high 5-year BCSS despite “unfavorable” age, tumor size, and grade (Table). 5-y BCSS for RS &amp;lt;11, by Clinicopathologic FactorsRS &amp;lt;11 and Age &amp;lt;50 yRS &amp;lt;11 and Tumor Size 2.1-5.0 cmRS &amp;lt;11 and Poor Tumor GradeN (% of N with CT ‘Yes’)5-y BCSS (95% CI)N (% of N with CT ‘Yes’)5-y BCSS (95% CI)N (% of N with CT ‘Yes’)5-y BCSS (95% CI)2009 (6.2%)100% (100%, 100%)1976 (5.5%)99.3% (98.5%, 99.7%)686 (5.8%)99.5% (97.9%, 99.9%) Conclusions: In this SEER population-based study, pts with RS &amp;lt;11 had a wide range of clinicopathologic features. 5-year BCSS was high (&amp;gt;99%), regardless of age, tumor size, or grade. These results support the new AJCC staging criteria that classify N0, HR+, HER2-negative pts with RS &amp;lt;11 and tumor size up to 5 cm as having Prognostic Stage IA disease. Citation Format: Baehner FL, Petkov VI, McCullough D, Shak S. Breast cancer-specific survival (BCSS) in SEER patients with 21-gene Recurrence Score® (RS) results &amp;lt;11 classified as prognostic stage IA by new 8th edition AJCC staging manual [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-03.

Abstract PD7-13: Molecular characterization and mortality from breast cancer in men

Abstract Background: Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Methods: We studied men and women with hormone receptor (HR)-positive breast cancer and 21-gene test (RS) results. Patients with negative nodes, micrometastasis, and 1-3 positive nodes were included. Differences in clinical characteristics and gene expression were determined and distribution of RS results was analyzed and correlated with 5-year breast cancer specific survival (BCSS) and overall survival (OS). Results: There were 3806 men and 571115 women. Men were older than women (mean age 64.2 vs. 59.1 years, p&amp;lt;0.001). RS &amp;lt;18 predominated in both genders, but RS ≥31 was more frequent in men (12.4% vs. 7.4%, p&amp;lt;0.001) as were very low scores (RS &amp;lt;11) (33.8% vs. 22.1%, p&amp;lt;0.001). Mean gene expression was higher in men for the ER, proliferation, and invasion groups. ER was lowest and PR highest in women &amp;lt;50 years, with a progressive increase in ER with age. Men &amp;lt;50 years had slightly lower ER and PR compared to older men. Survival data was available from SEER for 322 men and 55842 women. 5-year estimates for BCSS differed significantly between RS groups for both men (p=0.003) and women (p&amp;lt;0.001). For men, the 5-year BCSS was 99.0% and 95.9% with RS &amp;lt;18 and RS 18-30, respectively, and for women it was 99.5% and 98.6%, regardless of nodal status. RS ≥31 was associated with a 5-year BCSS of 81.0% in men and 94.9% in women. The prognostic utility of RS was evident in both men and women, despite the progressive increase in adjuvant chemotherapy use with higher RS results. 5-year BCSS and OS were overall lower in men than in women. Conclusion: This large genomic study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for 21-gene testing in both men and women, regardless of nodal status. Future adjuvant trials in ER-positive breast cancer should focus on targeting endocrine-resistance in those patients with RS ≥31, and need to consider the weight of competing causes of mortality when investigating the value of any additional treatment beyond endocrine therapy. Citation Format: Massarweh SA, Sledge GW, Miller DP, McCullough D, Petkov VI, Shak S. Molecular characterization and mortality from breast cancer in men [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-13.

Abstract P4-08-04: The clinical utility of oncotype Dx for patients with recurrence scores of 10 or less: A value based pathology study of tumor histopathology and outcomes analysis in an integrated delivery and finance health system

Abstract Introduction The majority of publications regarding breast cancer GEPTs rarely supply detailed breast tumor histopathology in their outcome studies. As a result, the cost effective role of clinical risk assessment with histopathology of breast carcinomas tends to be minimized. The aims of this study are to characterize the details of breast tumor histopathology of patients with Oncotype Dx Recurrence Scores (RS) of 10 or less, and determine if Oncotype Dx offers value and clinical utility for patients with these low grade tumors Methods A total of 459 patients (18%) with Oncotype Dx RS of 10 or less were retrieved from a registry of 2558 patients with Oncotype Dx results. Patients had five years of follow-up with tumor registry and were treated with endocrine therapy alone. Tissue slides were available to review on 441/459 patients. Recorded details included (1) histopathologic type of carcinoma (2) mitotic score (MS), tubule formation, nuclear pleomorphism and Notttingham histologc (NG) grade. (3) Estrogen (ER) and progesterone (PgR) semiquantitated by Allred Score and Histologic Score (H Score: strong 200-300, moderate 100-199, weak &amp;lt;100). (4) Lymph node status. (5) overall survival and breast cancer specific survival. Results Patient ages were 33-92, with mean/median age of 60, and all had endocrine therapy alone. 148 of 441(34%) patients had carcinomas of “special types”, notable for low grade/good prognosis including tubular 22(15%), cribriform 15 (10.1%), papillary 17 (11.5%), and mucinous 28 (21%), along with 63 (42.5%) low grade classic lobular carcinomas and 3 (2%) low grade mixed ductal and lobular carcinomas. All 148 tumors had a MS of 1, were NG1 and had high ER HScores (280 median/263 mean) (Allred Scores 7-8) and high PR HScores (210 median/201 mean) (Allred Scores 6-8). The remaining 293 tumors were ductal carcinomas of no special type (NST), and 261/293 (89%) of these had a MS of 1/NG2. Of the remaining cases, 10 (3%) had a MS of 2/NG2, 18 (6%) had MS of 2/NG3 and four (1%) were MS3/NG3. Estrogen receptor H Score/Allred Score was strong (Allred Score 7-8) in 395/441 (89.6%), moderate in 45 (10.2%) and weak in 1 patient (0.2%). Progesterone HScores were strong in (Allred Score 6-8) 269/441 (76%) and moderate in the remainder. Strong and moderate ER comprised 99.8% of tumors. Thus, tumors with MS1, and NG1, all with ER HScore &amp;gt;200 (Allred Score of 7-8) were enriched in the RS &amp;lt;10, and these features distinguished this group from other tumors with a MS1. At 5 years, 433 patients (98%) were alive, 8 were dead, 1 from breast cancer due to distant recurrence. The 5-year breast cancer specific survival for this group was 99.7%. [95%CI 98.5-99.9.] 87 cases were accrued in the ongoing prospective study to date. There were 15/87 (17%) cases, 95% of which were correctly identified by pathologists as having an RS &amp;lt;10 using the criteria defined, with sensitivity 95%, specificity 86%, PPV 63% 95% CI(49.76-75.08), NPV 99% 95% CI(90.7-99.78). No patient had a recurrence score &amp;gt;22. Conclusions Pathologists can identify these low risk tumors with high accuracy. Oncotype Dx lacks clinical value and utility in this setting. Citation Format: Dabbs DJ, Serdy K, Onisko A, Clark BZ, Bhargava R, Smalley S, Perkins S, Brufsky AM. The clinical utility of oncotype Dx for patients with recurrence scores of 10 or less: A value based pathology study of tumor histopathology and outcomes analysis in an integrated delivery and finance health system [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-08-04.

Abstract P3-01-01: Management of the axilla in metaplastic breast carcinoma

Abstract Background Metaplastic breast cancer (MBC), characterized by a mixture of epithelial, squamous or mesenchymal elements and a usually triple-negative (TN) phenotype, accounts for &amp;lt;1% of breast cancer diagnoses. MBC has a poor prognosis with frequent distant spread, but, paradoxically, a lower than expected rate of nodal positivity (6 to 40%). Due to its rarity there is little data on how best to evaluate and manage the axilla in women with these tumors. Thus we undertook this study to evaluate axillary management and oncologic outcomes. Methods With IRB approval, we identified adult patients diagnosed with MBC at our institution from 2001 to 2011 from our prospective surgical pathology database. Patient, pathology, imaging, treatment and outcome data were obtained from electronic medical record, tumor registry, pathology slide and imaging review. Median follow-up for surviving patients was 66 months. Statistical analyses were performed using JMP 10.0 software. Results We identified 41 MBC patients, median age 60 years (range 33-89 years), with a median tumor size of 2.7 cm; 33 (80%) were TN. 23 patients (56%) had a preoperative axillary ultrasound (AUS): 9 (39%) showed at least one suspicious axillary lymph node (LN) of whom 6 had a preoperative fine needle LN biopsy (FNA) of which 3 were positive for metastasis. 6 patients, including the 3 LN+ on FNA, had neoadjuvant chemotherapy (NAC). Operation included axillary dissection (ALND) in 14, sentinel LN biopsy (SLNB) in 23, and SLNB followed by ALND in 1, while 3 patients had no axillary surgery. 10 patients were LN+ at operation. Among 22 patients who had both an AUS and axillary surgery, AUS had a sensitivity of 100% and specificity of 78%. Patient and tumor variables in association with pathologic LN status are summarized in the table. LN positivity correlated with increasing tumor size, T stage, grade and angiolymphatic invasion. 16 patients recurred, most with distant disease (10/16, 63%), although there was a solitary axillary recurrence 8 months after a negative SLNB in one patient who did not have a preoperative AUS. Thus the accuracy of SLNB was 96% (23/24) overall, but among those without preoperative AUS, 1/7 (14%) SLNBs were falsely negative. 5-year disease-free and breast cancer-specific survival estimates were 49% and 63%. LN- N=28 (74%)LN+ N=10 (26%)p-valueSize, median (IQR), cm2.7 (1.6-4.6)6.6 (2.5-16.5)0.001T stage 0.03T19 (100%)0 (0%) T214 (78%)4 (22%) T33 (60%)2 (40%) T42 (33%)4 (67%) Grade 0.04Low6 (16%)0 (0%) Intermediate/High22 (58%)10 (26%) Estrogen Receptor 0.61Positive (&amp;gt;1%)5 (71%)2 (29%) Negative (&amp;lt;1%)23 (74%)8 (26%) Angiolymphatic Invasion 0.002No26 (87%)4 (13%) Yes2 (25%)6 (75%) Dominant Histology 0.65Adenosquamous2 (100%)0 (0%) Matrix producing4 (80%)1 (20%) Spindle cell14 (74%)5 (26%) Squamous*8 (67%)4 (33%) *any squamous component Conclusion Our study is the first to specifically address AUS and SLNB for patients with metaplastic breast cancer. AUS had 100% sensitivity and 78% specificity, while one patient without a preoperative AUS had a falsely negative SLNB. Further, AUS with FNA of suspicious LNs was useful for staging at the time of diagnosis and informing treatment. We recommend this approach for patients with MBC. Citation Format: Murphy BL, Fazzio RT, Hoskin TL, Glazebrook KN, Keeney MG, Habermann EB, Hieken TJ. Management of the axilla in metaplastic breast carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-01.

Ischaemic heart disease following conventional and hypofractionated radiation treatment in a contemporary breast cancer series.

We report the incidence of ischaemic cardiac toxicity in a contemporary cohort of patients receiving conventional (CFRT) or hypofractionated (HFRT) radiation after surgery for early breast cancer and investigate the interplay of cardiac risk factors and fractionation. Included were patients receiving external beam radiation treatment from 2002 to 2006 at the Christchurch public hospital. Hospital coding databases, oncology databases and medical records were reviewed for baseline characteristics, treatment details and outcomes. The primary outcome was cardiac toxicity (including myocardial infarction, admission for cardiac chest pain, coronary angiogram positivity and ischaemic cardiac death). Kaplan-Meier methods were used to derive ischaemic cardiac event free and overall survival. Predefined univariate and multivariate analysis was performed to investigate interaction with radiation fraction size, cardiac risk factors, age and side of cancer. Standardised mortality ratios were constructed. Five hundred and one patients were identified, 220 treated with CFRT and 281 with HFRT. The median age was 56 and median follow-up 10.33 years. The 10-year breast cancer specific survival was 81.8% (95% CI %.78.1-85.0). The 10-year freedom from cardiac death was 98.6% (95% CI 96.9-99.4). There were 27 post radiation cardiac events including 5 cardiac deaths and 19 cases of acute myocardial infarction. 265 (53%) had at least one cardiac risk factor. Twenty five of the 27 patients with a cardiac event had cardiac risk factors. On univariate and multivariate analysis, fractionation schedule was not significantly associated with a post radiation ischaemic event, however, there was a significant relationship with age and the presence of a cardiac risk factor. The standardised mortality ratio was 0.89 (95% CI: 0-3.13). Our study has shown a low rate of ischaemic cardiac disease for both CFRT and HFRT in women treated for breast cancer with no evidence of an effect with fractionation schedule. Coexisting cardiac risk factors are common in the population.

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.].

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.

Nestin expression in breast cancer: association with prognosis and subtype on 3641 cases with long-term follow-up.

Basal-like breast cancers, originally recognized by gene expression profiling, can be clinically identified using immunohistochemical (IHC) definitions that require estrogen receptor (ER) negativity. However, some basal cases are ER positive and are mistakenly considered to be luminal by standard IHC approaches, leading to suboptimal treatment choices. Nestin, an intermediate filament expressed in many stem cells, is a recently identified positive marker of basal-like phenotype independent of ER status. In this study, we evaluated its clinical associations and prognostic capacity in a large breast cancer cohort. A tissue microarray series of clinically annotated invasive breast cancers with 12.6-year median follow-up was assessed for nestin expression by IHC. Kaplan-Meier and Cox regression models were used to evaluate the prognostic significance of nestin status, for the primary endpoint of breast cancer-specific survival (BCSS). Among 3641 cases interpretable for nestin by IHC, positive staining was found in 371 cases (10%) and was significantly associated with poor prognostic factors including other markers of basal-like differentiation. Patients with nestin-positive tumors had a significantly lower 10year BCSS (HR 1.97, 95% CI 1.62-2.40; P<0.001). Importantly, within the large group of 2323 ER+cases, nestin positivity identified a subgroup of 120 patients (5%) with a significantly inferior 10-year BCSS (HR 1.50, 95% CI 1.10-2.13; P=0.02). Nestin IHC positivity is associated with the poor clinical outcomes and reduced survival rates that characterize the gene expression basal-like subtype. This easily applicable tool identifies ER+poor prognosis basal phenotype patients that are currently being missed by "Triple negative" or "Core basal" IHC definitions.

Influence of Biologic Subtype of Inflammatory Breast Cancer on Response to Neoadjuvant Therapy and Cancer Outcomes

BackgroundFew data exist on the influence of tumor biologic subtype on treatment response and outcomes for inflammatory breast cancer (IBC). We examined a contemporary cohort of IBC patients treated with current targeted systemic therapies, selected on the basis of tumor biologic subtype, to evaluate pathologic treatment response and cancer outcomes across biologic subtypes. Patients and MethodsWe studied 57 clinical stage T4dM0 IBC patients operated on at our institution from October 2008 to July 2015. Comparisons across biologic subtypes were performed by Wilcoxon rank-sum or chi-square tests; Kaplan-Meier and log-rank tests were used to analyze survival outcomes. ResultsAll patients received neoadjuvant systemic therapy; 54 (95%) completed postmastectomy radiation. Ninety-one percent (52/57) had clinically node-positive disease at presentation. Pathologic complete response (pCR) rates in the breast and axilla differed significantly by approximated biologic subtype, defined as estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER-2) negative; and HER-2 positive and ER negative/HER-2 negative (all P < .001). After 50 months' median follow-up, 20 patients experienced disease recurrence. Site of first relapse was distant in 80% (16/20). Disease-free survival (DFS) and breast cancer-specific survival (BCSS) differed significantly by biologic subtype. Five-year DFS was 46% for patients with ER-positive/HER-2–negative tumors, 82% for HER-2–positive tumors, and 33% for ER-negative/HER-2–negative tumors (P < .001), while 5-year BCSS was 76%, 100%, and 57%, respectively (P = .02)—notably better than historic reports. ConclusionOur data show that both treatment response and outcomes vary significantly across IBC biologic subtypes. Multimodal treatment and modern systemic therapies have markedly improved DFS and BCSS. These data provide further evidence to suggest that IBC is not a distinct biologic entity transcending standard breast tumor marker subclassification.

Postoperative radiotherapy for invasive micropapillary carcinoma of the breast: an analysis of Surveillance, Epidemiology, and End Results database.

IntroductionInvasive micropapillary carcinoma (IMPC) of the breast poses a high risk of locoregional recurrence, and postoperative radiotherapy (PORT) may be beneficial in IMPC. Hence, we determined the clinical value of PORT in IMPC patients.Patients and methodsWe assessed clinicopathological factors extracted from the Surveillance, Epidemiology, and End Results database (2004–2013). Univariate and multivariate Cox proportional hazards regressions were performed to assess the independent prognostic factors on breast cancer-specific survival (BCSS) and overall survival (OS).ResultsOf the 881 study patients, 444 (50.4%) and 437 (49.6%) underwent breast-conserving surgery (BCS) and mastectomy (MAST), respectively, of whom 357 (80.4%) and 153 (35.0%) underwent PORT, respectively. Patients with young age, large tumor size, or advanced nodal stage were more likely to undergo MAST and PORT compared with MAST alone. Patients with progesterone receptor-positive disease were more likely to receive BCS and PORT compared with BCS alone. The 5-year BCSS and OS were 95.7% and 90.9%, respectively. On multivariate analyses, tumor size, histological grade, and estrogen receptor status were independent predictors of BCSS and OS. The types of surgical procedures (MAST vs. BCS) were not an independent predictor of survival outcomes. Patients who underwent MAST with or without PORT had similar BCSS and OS in the multivariate analyses. Those who underwent BCS plus PORT did not have better BCSS and OS than those who underwent BCS alone. In the low-, intermediate-, and high-risk groups, PORT was not associated with better BCSS and OS than non-PORT groups in patients who received BCS or MAST.ConclusionIMPC has favorable BCSS and OS. Regardless of the types of surgical procedures (MAST or BCS), PORT groups were not inferior to non-PORT groups on BCSS and OS.

Tumor Biology and Response to Chemotherapy Impact Breast Cancer-specific Survival in Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: Long-term Follow-up From ACOSOG Z1071 (Alliance).

Women with node-positive breast cancer are at high risk for recurrence. We evaluate the impact of approximated tumor subtype and response to chemotherapy on long-term outcomes in a node-positive cohort receiving neoadjuvant chemotherapy. ACOSOG Z1071 enrolled cT0-4N1-2 breast cancer patients treated with neoadjuvant chemotherapy from 2009 to 2011. Factors impacting breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed. Median follow-up of 701 eligible patients was 4.1 years (0.4-6.5). Ninety patients (12.8%) died from breast cancer. Approximated subtype and chemotherapy response were significantly associated with BCSS and OS (P < 0.0001). BCSS and OS were highest in patients who achieved pathologic complete response (pCR) (P < 0.0001 and P < 0.0001, respectively).Five-year BCSS was highest in human epidermal growth factor receptor 2 (HER2)-positive disease [95.8%; 95% confidence interval (CI): 87.7-98.6], followed by hormone receptor-positive/HER2-negative (80.4%; 95% CI: 73.2-85.9) and lowest in triple-negative (TNBC) (74.8%; 95% CI: 66.6-81.2; P < 0.0001). Similar patterns were seen in OS.In TNBC (n = 174), 5-year BCSS was higher in patients with pCR versus residual disease (89.8%; 95% CI: 78.8-95.3 vs 65.8%; 95% CI: 54.5-74.9; P = 0.0013). In hormone receptor-positive/HER2-negative (n = 318) disease, BCSS was 100% in patients with pCR and 78.3% (95% CI: 70.4-84.3) in those with residual disease (P = 0.018). In HER2-positive disease (n = 204) there was no difference between pCR and residual disease (96.0%; 95% CI: 83.6-99.1 vs 95.8%; 95% CI: 81.4-99.1; P = 0.77). In node-positive breast cancer patients treated with neoadjuvant chemotherapy, BCSS and OS were associated with approximated subtype and chemotherapy response and were lowest in TNBC patients with residual disease. Five-year BCSS was > 95% in HER2-positive disease independent of chemotherapy response.

The Impact of Young Age for Prognosis by Subtype in Women with Early Breast Cancer

Young age (≤40 years) use to be considered an independent risk factor for the prognosis of women with early-stage breast cancer. We conducted a retrospective analysis to investigate this claim in a population of young patients who were stratified by molecular subtype. We identified 2,125 women with stage I to III breast cancer from the Fujian Medical University Union Hospital. Multivariable Cox proportional hazards models were used to analyze the relationship between age groups stratified by molecular subtype and 5-year disease-free survival (DFS), 5-year distant metastasis-free survival (DMFS), and 5-year breast cancer-specific survival (BCSS). Median follow-up time was 77 months. Patients ≤40 years of age presented with a significantly worse 5-year DFS and 5-year DMFS. In stratified analyses, young women with luminal A subtype disease were associated with a worse 5-year DFS, 5-year DMFS, and 5-year BCSS. Women with luminal B (Her2−) tumors showed a decrease in 5-year DFS and 5-year DMFS. Our findings support the hypothesis that young age seems to be an independent risk factor for the prognosis for breast cancer patients with the luminal A and luminal B (Her2−) subtypes but not in those with luminal B (Her2+), Her2 over-expression, and triple-negative disease.

Better survival after breast-conserving therapy compared to mastectomy when axillary node status is positive in early-stage breast cancer: a registry-based follow-up study of 6387 Norwegian women participating in screening, primarily operated between 1998 and 2009

BackgroundRecent registry studies on early-stage breast cancer have shown better survival rates when women underwent breast-conserving therapy (BCT) compared with mastectomy (MTX). The aim of this study is to investigate women participating in screening, in all four stages of early breast cancer (T1N0M0, T2N0M0, T1N1M0, and T2N1M0), as to whether there is a survival benefit when women undergo BCT compared to MTX.MethodA cohort of 6387 women aged 50–69, with primary-operated breast cancer from January 1998 to December 2009, participating in screening and followed-up until the end of 2010. Life tables were calculated by stages (pT1N0M0, pT2N0M0, pT1N1M0, and pT2N1M0), surgery groups (BCT and MTX), and screening detection (first screening, later screening, or interval cancer). Cox regression was used to calculate hazard ratios (HR) between BCT and MTX in crude and adjusted analyses.ResultsIn stage T1N1M0, women who underwent MTX had an HR of 2.91 (95% CI 1.30–6.48) for breast cancer death compared to women who underwent BCT, after adjusting for screening detection, years of diagnosis, age at diagnosis, histology, grade, and hormone receptor status. For all other TNM categories of early breast cancer, there was no difference in survival.10-year breast cancer-specific survival (BCSS) in T1N0M0 was 98% for women undergoing BCT and 96% for women undergoing MTX. 10-year BCSS in T1N1M0 was 97% for women undergoing BCT and 89% for women undergoing MTX.ConclusionsFor women participating in screening, there is a benefit of BCT over MTX in stage T1N1M0. No such effects were observed in the other early stages of breast cancer.

Abstract 2258: Genome-wide association studies of breast cancer prognosis

Abstract Introduction: The prognosis and response to treatment in women with breast cancer varies considerably after taking into account clinic-pathological variables. Other factors such as host genotype are also likely to be important. We therefore investigated the role of germline genetic variation on survival after breast cancer using data from the Breast Cancer Association Consortium. Materials and methods: We included data from ten projects in which breast cancer case cohorts were genotyped using arrays providing genome-wide coverage of common variants. The majority of samples was genotyped using the Illumina custom iCOGS or OncoArray chips. Data were imputed using the 1000 Genome phase 3 as a reference panel using a two-stage procedure. We assessed the association between genotype and 10-year breast cancer specific survival for each SNP using Cox proportional hazards regression adjusted for principle components and stratified by country. Genotype data from 87,877 breast cancer cases, 63,170 ER-positive and 20,297 ER-negative, with 6,511 known breast cancer deaths were included in the analyses. Results: Preliminary analyses shows that in all invasive cases, ER-positive and ER-negative disease 123, 110, and 212 variants respectively, were associated with breast cancer-specific mortality at P&amp;lt;5x10-5. A single variant, rs1295683, was associated with higher mortality at genome-wide significance in all patients: HR=1.16 (95%CI:1.10-1.22); P=2.8x10-8 (risk allele frequency: 0.12). We identified four variants to be associated with mortality in ER-negative disease at P&amp;lt;5x10-8. The strongest association was for rs145963877: HR=1.32 (95%CI:1.20-1.46); P=2.3x10-8. No variant reached genome-wide significance for ER-positive disease; the most significant variant was chr7:41400313 with an HR=1.17 (95%CI:1.10-1.24); P=1.8x10-7. In addition, using OncoArray data, we provided independent validation of higher mortality of CHEK2 c.1100delC carriers compared with non-carriers (HR=1.56 (95%CI:1.22-2.01)), previously reported in Weischer et al JCO 2012. Using iCOGS data, we evaluated the association between mortality and the polygenic risk score (PRS) based on 77 known breast cancer susceptibility SNPs. A higher PRS was significantly associated with lower breast cancer-specific mortality: HR=0.87(95%CI:0.81-0.93) (per unit of PRS) with a similar association in ER-negative and ER-positive disease. The association was attenuated after adjusting for tumor grade. Conclusion: We have identified a novel set of germline genetic variants that are associated with breast cancer prognosis. The effect sizes are small for each of the variants and unlikely to be of immediate clinical relevance. However, understanding of the biology that underlies the associations may identify novel pathways and targets for therapy. Being at higher risk of breast cancer, as defined by the breast cancer susceptibility PRS, is not associated with an adverse prognosis. Citation Format: Marjanka K. Schmidt, Qi Guo, Thilo Dörk, Diana Eccles, Renske Keeman, Jacques Simard, Peter Kraft, Douglas F. Easton, Paul D. Pharoah, on behalf of the Breast Cancer Association Consortium. Genome-wide association studies of breast cancer prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2258. doi:10.1158/1538-7445.AM2017-2258