Detection and significance of small and low proliferation breast cancer

2021 ◽  
pp. 096914132110239
Author(s):  
Solveig Hofvind ◽  
Gøril Knutsvik ◽  
Åsne S Holen ◽  
Kaitlyn M Tsuruda ◽  
Lars A Akslen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Small Diameter ◽  
Rank Test ◽  
Tumor Diameter ◽  
Cancer Death ◽  
Breast Cancers ◽  
Breast Cancer Death ◽  
Cancer Management

Objectives To determine the frequency and discuss possible implications of early breast cancer with particularly good prognosis and defined by tumor diameter and cell proliferation. Setting Detection of small and slowly growing tumors presents a challenge in breast cancer management, due to the risk of over-treatment. Here, we attempted to define a group of such tumors by combining small diameter (≤10 mm, T1ab tumors) with low tumor cell proliferation (≤10% Ki67 expression rate). These tumors were termed small low proliferation cancers (SLPC). Methods Two population-based cohorts were studied: a small research series ( n = 534), and a nation-wide registry-based series of prospectively collected routine data ( n = 8433). In the latter, we stratified by detection mode; screen-detected, interval, and breast cancers detected outside of screening. Patients were treated according to national guidelines at time of their diagnosis. For both cohorts, we compared tumor histopathology and risk of breast cancer death using a log-rank test for cases with SLPC versus non-SLPC. Results In the research series (median follow-up 151 months), the frequency of SLPC was 10% (54/534), with one breast cancer death compared with 78 among the remaining 480 cases of non-SLPC ( p = 0.008). In the registry series (median follow-up 42 months), the frequency of SLPC was 10% (854/8433), with five deaths compared to 187 among the remaining 7579 cases ( p = 0.0004). Conclusions SLPC was associated with very low risk of breast cancer death. Prospective randomized trials are needed to clarify whether less aggressive treatment could be a safe option for women with such early breast cancers.

Is Breast Cancer Ever Cured? Follow-Up Study of 5623 Breast Cancer Patients

1991 ◽  
Vol 77 (6) ◽  
pp. 465-467 ◽  
Author(s):  
Stefano Ciatto ◽  
Rita Bonardi
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Systemic Disease ◽  
Cancer Death ◽  
Breast Cancer Patients ◽  
Death Rates ◽  
Breast Cancer Death ◽  
Long Term Follow Up

The authors evaluated 5623 cases of primary breast cancer followed for 1 to 21 years. Overall and breast cancer death rates were determined and compared to expected rates. Breast cancer patients showed overall and breast cancer death rates significantly higher than expected and which persisted at long-term follow-up. The observed/expected overall death ratios for follow-up periods of 0–5, 6–10, 11–15 or 16–20 years were 3.61, 2.55, 1.60 and 2.11, respectively. Death rates from breast cancer at 5, 10, 15 and 20 years were 20%, 32%, 40% and 48% respectively. The evidence of a persistent excess mortality even after long-term follow-up suggests the hypothesis that breast cancer is a systemic disease when clinically diagnosed. This study provided no evidence of a « clinical » cure for breast cancer patients. Even for N- patients the 5, 10, 15 and 20 year death rates from breast cancer were 12%, 20%, 28% and 38%, respectively. N- breast cancer, which is currently considered as a localized disease cured by surgery in most cases, would be better regarded to as a slow-growing metastatic disease, although « personal » cure may be achieved in many subjects dying of causes other than breast cancer.

Ten-Year Outcomes in a Population-Based Cohort of Node-Negative, Lymphatic, and Vascular Invasion–Negative Early Breast Cancers Without Adjuvant Systemic Therapies

2004 ◽  
Vol 22 (9) ◽  
pp. 1630-1637 ◽  
Author(s):  
Stephen K. Chia ◽  
Caroline H. Speers ◽  
Cicely J. Bryce ◽  
Malcolm M. Hayes ◽  
Ivo A. Olivotto
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Population Based ◽  
Adjuvant Systemic Therapy ◽  
Breast Cancers ◽  
Node Negative ◽  
Breast Cancer Death ◽  
Cancer Death Rate ◽  
Breast Cancer Death Rate

Purpose To discuss the absolute benefits from adjuvant systemic therapy knowledge of long-term outcomes and baseline risks of relapse and disease-specific survival are required. We assessed the 10-year outcomes in a population-based cohort of node-negative (N−) lymphovascular negative (LV−) early breast cancers diagnosed from 1989 to 1991 who did not receive adjuvant systemic therapy. Methods One thousand one hundred eighty-seven cases of pT1–2N0 LV− breast cancers with a median follow-up of 10.4 years were reviewed. Kaplan-Meier survival curves for relapse free survival (RFS), breast cancer–specific survival (BCSS) and overall survival (OS) were compared with log-rank tests with cohorts stratified for tumor size and grade. Results The median age of this series was 62 years. Four hundred thirty tumors were ≤ 1 cm in diameter (cohort 1), 507 were 1.1–2 cm (cohort 2), and 250 were 2.1 to 5 cm in diameter (cohort 3). The 10-year outcomes for cohorts 1, 2, and 3, respectively, were significantly different: RFS, 82%, 75%, and 66%; BCSS, 92%, 90%, and 77%; and OS, 79%, 78%, and 66%. Tumor grade significantly altered outcome within size cohorts, particularly in pT1N0 breast cancers. Conclusion This study provides detailed information on the continued relapse and breast cancer death rate to 10 years of follow-up. Specifically, without adjuvant systemic therapy, patients with LV−, N − breast cancer had a ≥ 25% 10-year risk of relapse and a corresponding 10-year breast cancer death rate of ≥ 10% if they had either a grade 3 tumor ≤ 1 cm, a grade 2 to 3 tumor from 1.1 to 2 cm, or any grade tumor greater than 2 cm.

scholarly journals Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dechuang Jiao ◽  
Jingyang Zhang ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
Yue Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Model ◽  
Survival Rates ◽  
Tumor Grade ◽  
Population Based ◽  
Rank Test ◽  
Breast Cancers ◽  
Significant Independent Predictor ◽  
Cancer Specific Survival ◽  
7Th Edition

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

scholarly journals Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 636 ◽  
Author(s):  
Regina Padmanabhan ◽  
Hadeel Shafeeq Kheraldine ◽  
Nader Meskin ◽  
Semir Vranic ◽  
Ala-Eddin Al Moustafa
Keyword(s):  
Breast Cancer ◽  
Mathematical Models ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Breast Cancers ◽  
Treatment Protocols ◽  
Cancer Subtypes ◽  
Cancer Management ◽  
Her2 Breast Cancer ◽  
Programmed Death

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

scholarly journals Assessment of the Accuracy of the Gail Model in Women With Atypical Hyperplasia

2008 ◽  
Vol 26 (33) ◽  
pp. 5374-5379 ◽  
Author(s):  
V. Shane Pankratz ◽  
Lynn C. Hartmann ◽  
Amy C. Degnim ◽  
Robert A. Vierkant ◽  
Karthik Ghosh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Health Care Professionals ◽  
Breast Disease ◽  
Develop Breast Cancer ◽  
Atypical Hyperplasia ◽  
Individual Risk ◽  
Breast Cancers ◽  
Gail Model ◽  
Patient Counseling

Purpose An accurate estimate of a woman's breast cancer risk is essential for optimal patient counseling and management. Women with biopsy-confirmed atypical hyperplasia of the breast (atypia) are at high risk for breast cancer. The Gail model is widely used in these women, but has not been validated in them. Patients and Methods Women with atypia were identified from the Mayo Benign Breast Disease (BBD) cohort (1967 to 1991). Their risk factors for breast cancer were obtained, and the Gail model was used to predict 5-year–and follow-up–specific risks for each woman. The predicted and observed numbers of breast cancers were compared, and the concordance between individual risk levels and outcomes was computed. Results Of the 9,376 women in the BBD cohort, 331 women had atypia (3.5%). At a mean follow-up of 13.7 years, 58 of 331 (17.5%) patients had developed invasive breast cancer, 1.66 times more than the 34.9 predicted by the Gail model (95% CI, 1.29 to 2.15; P < .001). For individual women, the concordance between predicted and observed outcomes was low, with a concordance statistic of 0.50 (95% CI, 0.44 to 0.55). Conclusion The Gail model significantly underestimates the risk of breast cancer in women with atypia. Its ability to discriminate women with atypia into those who did and did not develop breast cancer is limited. Health care professionals should be cautious when using the Gail model to counsel individual patients with atypia.

scholarly journals Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 743
Author(s):  
Oluwaseun Akinyele ◽  
Heather M. Wallace
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Growth Responses ◽  
Cancer Management ◽  
Mcf 7

Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

2008 ◽  
Vol 26 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Marta Guix ◽  
Nara de Matos Granja ◽  
Ingrid Meszoely ◽  
Theresa B. Adkins ◽  
Bobbye M. Wieman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Preoperative Treatment ◽  
Breast Cancers ◽  
Tumor Cell Proliferation ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

scholarly journals FOLLOW-UP OF PATIENTS AND PROGNOSTIC IMPACT OF TUMOUR MARKER CA 15-3 ON PATIENTS OF BREAST CANCER: A RETROSPECTIVE COHORT STUDY

2020 ◽  
Vol 8 (11) ◽  
pp. 656-660
Author(s):  
Anjali Vinocha ◽  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Cancer Patients ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Relative Survival ◽  
Rank Test ◽  
Prognostic Impact ◽  
Breast Cancer Patients

Introduction:Breast cancer is the most common cancer in women, with 5- and 10-year relative survival rates are 91% and 84%, respectively for women with invasive breast cancer. This study aimed to detect the role of serum breast cancer marker CA 15-3 for early detection of metastasis, relapse or recurrence for management of breast cancer patients. Methods: It was a retrospective cohort study with a total of 132 breast cancer patients from the year 2010 to march 2020 were taken and followed up. For these patients demographic, biochemical parameters, radiological and clico-pathological data were collected and analysed. Result: The mean age at the time of presentation and mean duration of follow-up was 47 years and 31 months respectively. There was elevation in the serum level of CA 15-3 at the time of diagnosis of metastasis, recurrence or residual disease in 41 patients. This shows that sensitivity of elevated CA 15-3 (> 30 IU/ml) level in Ca Breast patients was 84%, 75 % and 75 % with respect to metastasis, recurrence and relapse. Log Rank test Chi- square value was 7.39 which was statistically significant (p=0.007). Cox proportional hazard model was created for effect of age at presentation, CA 15-3 at the time of diagnosis and MRM on distant metastasis and was statistically significant (p=0.037). Conclusion: We recommend that for the management of breast cancer patients, Cancer antigen (CA 15-3) levels can be used as prognostic marker for early diagnosis of metastasis, recurrence or relapse.

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