scholarly journals Pathogenic Variants in CHEK2 Are Associated With an Adverse Prognosis in Symptomatic Early-Onset Breast Cancer

2020 ◽  
pp. 472-485
Author(s):  
Stephanie L. Greville-Heygate ◽  
Tom Maishman ◽  
William J. Tapper ◽  
Ramsey I. Cutress ◽  
Ellen Copson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Young Patients ◽  
Disease Free Survival ◽  
Distant Disease ◽  
Free Survival ◽  
Pathogenic Variants ◽  
Symptomatic Breast Cancer ◽  
Disease Free ◽  
Associated Tumors

PURPOSE Checkpoint kinase 2 ( CHEK2) is frequently included in multigene panels. We describe the associated outcomes among carriers of CHEK2 pathogenic variants in young patients with symptomatic breast cancer. PATIENTS AND METHODS Participants (N = 2,344) in the Prospective Outcomes in Sporadic Versus Hereditary Breast Cancer study had a diagnosis of primary invasive breast cancer at age ≤ 40 years. Summary statistics were used to compare tumor characteristics among CHEK2+ carriers with those who were CHEK2−. Kaplan-Meier curves were used to demonstrate overall survival (OS) and distant disease-free survival. RESULTS Overall, 53 of the 2,344 participants (2.3%) had a pathogenic CHEK2 variant. CHEK2+-associated tumors were significantly more likely to be grade 2, estrogen receptor and progesterone receptor–positive compared with CHEK2− tumors (grade 2, n = 28 of 52 [53.8%] v n = 803 of 2,229 [36.0%]; P = .029). CHEK2-associated tumors were significantly more likely to have nodal involvement (N1, n = 37 of 53 [69.8%] v 1,169 of 2,253 [51.9%]; P = .0098) and demonstrated a trend toward multifocality. A higher proportion of participants with CHEK2+ variants with invasive breast cancer were obese than were those with CHEK2− variant (28.3% v 18.8%; P = .039). Univariate and multivariable analyses revealed that OS and distant disease-free survival were significantly worse in CHEK2+ versus CHEK2− carriers (OS hazard ratio, 1.58; 95% CI, 1.01 to 2.48; P = .043). CONCLUSION This work highlights the adverse prognosis associated with breast cancer in carriers of CHEK2 pathogenic variants. It also identifies a potential association among obesity, family history, and breast cancer risk in young CHEK2 gene carriers.

scholarly journals Factors Affecting Distant Disease-Free Survival for Primary Invasive Breast Cancer: Use of a Log-Normal Survival Model

2000 ◽  
Vol 7 (6) ◽  
pp. 416-426 ◽  
Author(s):  
David R. McCready ◽  
Judy-Anne W. Chapman ◽  
Wedad M. Hanna ◽  
Harriette J. Kahn ◽  
David Murray ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Disease Free Survival ◽  
Survival Model ◽  
Distant Disease ◽  
Free Survival ◽  
Factors Affecting ◽  
Primary Invasive Breast Cancer ◽  
Log Normal ◽  
Disease Free

scholarly journals Relationship between Ribosomal Protein S6-pS240 Expression and other Prognostic Factors in Non-Special Type Invasive Breast Cancer

Breast Care ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 171-175
Author(s):  
Frederik Cuperjani ◽  
Lumturije Gashi ◽  
Fisnik Kurshumliu ◽  
Shemsedin Dreshaj ◽  
Fitim Selimi
Keyword(s):  
Breast Cancer ◽  
Ribosomal Protein ◽  
Invasive Breast Cancer ◽  
Menopausal Status ◽  
Treatment Protocol ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free

Background: The aim of this study was to investigate the immunohistochemical expression of ribosomal protein (RP) S6-pS240 in non-special type invasive breast cancer in relation to other prognostic markers and gain new insights to facilitate more individualized treatment. Methods: The following clinical and histopathological parameters of 120 patients were determined: S6-pS240 expression, age, menopausal status, tumor size and grade, TNM stage, Nottingham Prognostic Index (NPI), lymph node stage, estrogen and progesterone receptor (ER/PR) expression, HER2/neu amplification, lymphovascular invasion, and proliferative index as measured by Ki-67. Treatment protocol and disease-free survival were evaluated accordingly. Results: Significant positive correlations were seen between S6-pS240 expression and Ki-67 values (rho = 0.530, p < 0.001), and NPI (rho = 0.370, p < 0.001) and HER2/neu amplification (rho = 0.368, p < 0.001). A negative correlation was found between S6-pS240 and ER/PR expression (rho = 0.362, p < 0.001). Patients with negative RP S6-pS240 expression had significantly longer disease-free survival (log-rank test, p = 0.005). Conclusion: Immunohistochemical analysis of RP S6-pS240 is a valuable additional prognostic marker in patients with invasive breast cancer. Routine use of S6-pS240 immunohistochemistry is recommended.

High Expression of Obesity-Linked Phosphatase SHIP2 in Invasive Breast Cancer Correlates with Reduced Disease-Free Survival

Tumor Biology ◽  
2008 ◽  
Vol 29 (5) ◽  
pp. 330-341 ◽  
Author(s):  
Nagendra K. Prasad ◽  
Manish Tandon ◽  
Anant Handa ◽  
George E. Moore ◽  
Charles F. Babbs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Disease Free Survival ◽  
High Expression ◽  
Free Survival ◽  
Disease Free

Clinical response at 4 months to neoadjuvant letrozole predicts distant disease free survival in postmenopausal women with stage II-III ER/PgR-positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10531-10531 ◽  
Author(s):  
V. Guillem ◽  
A. Llombart-Cussac ◽  
J. Lopez Guerrero ◽  
A. Guerrero ◽  
C. Fuster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Prognostic Indicators ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (<5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p < 0.02), cT3/4 (p < 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p < 0.05), cN (p < 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.

scholarly journals SPECIAL APPROACHES TO BREAST CANCER HORMONAL THERAPY OF YOUNG PATIENTS

2016 ◽  
Vol 7 (2) ◽  
pp. 15-20
Author(s):  
D N Kravchenko ◽  
A A Parokonnaya ◽  
M I Nechushkin ◽  
D E Avtomonov
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Young Patients ◽  
Disease Free Survival ◽  
Free Survival ◽  
Ovarian Suppression ◽  
Prognostic Features ◽  
Disease Free Survival Rate ◽  
Disease Free

Breast cancer is the most prevalent female malignancy. When diagnosed at young age (up to 40 years), negative clinical, morphological and prognostic features are noted. A non-randomized retrospective trial (n=500) was performed to evaluate different scenarios of breast cancer hormone therapy in young patients. Ovarian suppression in young patients is shown to statistically improve prognosis. Disease-free survival rate values are observed to decrease in patients without ovarian suppression in comparison with any type of ovarian suppression, especially at a remote follow-up (after 60 months). Menstrual function resumption and no amenorrhea after chemotherapy significantly decrease disease-free survival rate values in young patients.

Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes

2002 ◽  
Vol 20 (5) ◽  
pp. 1304-1310 ◽  
Author(s):  
Roman Rouzier ◽  
Jean-Marc Extra ◽  
Jerzy Klijanienko ◽  
Marie-Christine Falcou ◽  
Bernard Asselain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Primary Chemotherapy ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Bryan P. Schneider ◽  
Guanglong Jiang ◽  
Tarah J. Ballinger ◽  
Fei Shen ◽  
Christopher Chitambar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free ◽  
Versus Treatment ◽  
Tumor Dna

PURPOSE Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). PATIENTS AND METHODS From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. RESULTS One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. CONCLUSION Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.

Sign in / Sign up

Export Citation Format

Share Document