Tumor characteristics and recurrence patterns in triple negative breast cancer: A comparison between younger (<65) and elderly (⩾65) patients

doi:10.1016/j.ejca.2012.04.019

European Journal of Cancer

Volume 48, Issue 16, November 2012, Pages 2962-2968

https://doi.org/10.1016/j.ejca.2012.04.019 Get rights and content

Abstract

Background

In an aging population an increasing number of breast cancers is diagnosed in elderly women. Tumor characteristics and patterns of metastasation have been extensively elucidated in younger triple negative breast cancer (TNBC) patients, but data regarding TNBC in elderly women are missing. The goal of this investigation was to compare clinical pathological characteristics of younger and elderly TNBC patients in order to assess their relevance for TNBC in an aging population.

Methods

Data of TNBC patients diagnosed between 1998 and 2004 were retrospectively analyzed by computer based chart information. Baseline tumor characteristics, patient demographics and patterns of metastasation were compared between younger (<65 years) and elderly (⩾65 years) TNBC patients.

Results

Out of 254 TNBC patients 75.6% were <65 years and 24.4% were ⩾65 years. Mean tumor size, tumor grade and number of positive lymph nodes did not differ significantly (p = 0.865, 0.115 and 0.442, respectively) between both age groups. Distant visceral metastases occurred significantly more often than bone metastases in both age groups (p < 0.001). Local recurrences, bone and secondary lymph node metastases were observed at significantly higher numbers in younger patients (p = 0.035, 0.025 and 0.041, respectively). Elderly TNBC patients received significantly less chemotherapy than younger patients (p < 0.001).

Conclusions

TNBC of elderly patients is an aggressive breast cancer subtype claiming as much attention as TNBC in younger patients, thus warranting chemotherapeutic intervention irrespectively of age.

Introduction

Breast cancer incidence increases with age. More than half of the newly diagnosed breast cancer patients are aged ⩾65 years.¹ Elderly breast cancer patients are less likely to receive breast cancer surgery, radiation or chemotherapy.2, 3 Noticing the increasing importance of elderly breast cancer patients in an aging population, recent studies describe the benefit to standard antineoplastic therapy in breast cancer patients ⩾65 years.4, 5 Only 7% and 3% of patients aged >65 and >70 years, respectively, are represented in clinical studies.⁶ It has been proposed that life expectancy and co-morbidities should guide treatment decisions in each patient category, because an average 65-year-old patient without co-morbidities has a life expectancy of approximately 20 years and should therefore receive state of the art treatment for breast cancer. Seventy years or older might be the more appropriate definition of elderly patients nowadays. However, not only patients aged 70 years and older, but as well patients 65 years and older are a heterogeneous group, where a key issue are the co-morbidities of the patients.7, 8

Although it had been described that elderly women are more likely to have steroid receptor positive tumors and to be Her/2neu negative, numerous elderly breast cancer patients belong to the aggressive triple negative breast cancer (TNBC) subtype.9, 10

The hallmark of TNBC is a lack of estrogen receptor (ER), progesterone receptor (PR) and missing Her2/neu overexpression.11, 12 TNBC patients are a clinically highly relevant patient group that is characterised by younger age, unfavourable histopathological features including high histological grade, elevated mitotic count and pushing margins of invasion with a shortened overall survival (OS) and disease free survival (DFS) compared to other breast cancer subgroups. In younger women TNBC has been described to occur more often with a high risk of recurrence and death, respectively, the latter with a peak incidence of 3 years after primary diagnosis.¹³ The pattern of recurrence involves more often visceral organs and less common bones compared to other breast cancer subtypes.¹⁴ The available knowledge of clinical pathological parameters in TNBC patients <65 years of age provides a solid basis for risk estimation and performing treatment proposals. Although some reviews regarding breast cancer patients ⩾70 years of age and randomized studies including breast cancer patients ⩾65 years of age have recently been published, tumor characteristics, patient demographics and patterns of metastasation in TNBC patients ⩾65 years and older are still an area of uncertainty.7, 15

The aim of this investigation is to compare tumor characteristics, patient demographics and patterns of metastasation between younger and older TNBC patients to deepen the experience with TNBC in an aging population. The solid knowledge of these factors in younger TNBC patients allows a direct comparison with that in their elderly counterparts and shall allow assessing their relevance for TNBC in elderly women.

Section snippets

Study population

Between 1998 and 2004 patients with primary breast cancer were diagnosed and treated at the Department of Obstetrics and Gynaecology, Medical University of Vienna, Austria. Surgery and adjuvant or neo-adjuvant chemotherapy were performed at the same institution. Triple-negativity of primary breast cancers was identified in a retrospective manner by computer based chart information. Patients were excluded if they had ductal carcinoma in situ, secondary malignancies, recurrent breast cancer,

Demographics and tumor characteristics

Overall 254 Caucasian TNBC patients were included in this retrospective analysis. Eighty-nine (35.0%) and 165 (65.0%) TNBC patients were pre- and postmenopausal (p < 0.001), respectively. Mean age was 54.1 years (range 29–85 years) in the overall TNBC patient group. The mean age for TNBC paitents <65 years at diagnosis was 48.45 years (range 29–64 years) and 71.6 years (range 65–89 years) for the elderly (p < 0.0001). Thirty-nine (15.3%) TNBC patients were ⩾70 years of age. More detailed age categories are

Discussion

It was the aim of this investigation to compare the tumor characteristics, patient demographics and patterns of metastasation between younger and elderly women harbouring the specific TNBC subtype. TNBC of the elderly is of even more actuality because breast cancer incidence increases with age as it affects one out of 14 women aged 60–79 years.²¹ Generally an age of over 70 years is suggested to define the elderly patient. Nevertheless, an age cut-off ⩾65 years was chosen to define the elderly

Role of the funding score

The views expressed in the article are those of the authors and not of Ratiopharm. Ratiopharm did not influence the study concept, the study design, data acquisition, data analysis and data interpretation.

Conflict of interest statement

None declared.

Acknowledgements

This investigation was supported by Applied Cancer Research – Institution for Translational Research Vienna (ACR-ITR VIEnna) and was partly funded by Ratiopharm.

References (36)

L. Biganzoli et al.
Management of elderly individuals with breast cancer: update of the recommendations of the International Society of Geriatric Oncology (SIOG) and the European Society of Breast Cancer Specialists (EUSOMA)
Lancet Oncol
(2012)
C.A. Livasy et al.
Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma
Mod Pathol
(2006)
H.B. Muss et al.
Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer
JAMA
(2005)
M.A. Schonberg et al.
Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival
J Clin Oncol
(2010)
X. Du et al.
Patterns of use of chemotherapy for breast cancer in older women: findings from Medicare claims data
J Clin Oncol
(2001)
H.B. Muss et al.
Adjuvant chemotherapy in older women with early-stage breast cancer
N Engl J Med
(2009)
C. Bouchardy et al.
Undertreatment strongly decreases prognosis of breast cancer in elderly women
J Clin Oncol
(2003)
H.B. Muss
Adjuvant treatment of elderly breast cancer patients
Breast
(2007)
H.B. Muss
Coming of age: breast cancer in seniors
Oncologist
(2010)
A. Ring et al.
Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the arimidex, tamoxifen alone or in combination trial
J Clin Oncol
(2011)

S.G. Diab et al.

Tumor characteristics and clinical outcome of elderly women with breast cancer

J Natl Cancer Inst

(2000)

W.C. Taylor et al.

Recent advances: adjuvant therapy for older women with breast cancer

Cancer J

(2010)

A. Berghoff et al.

Brain metastases free survival differs between breast cancer subtypes

Br J Cancer

(2012 Jan 31)

W.D. Foulkes et al.

Triple-negative breast cancer

N Engl J Med

(2010)

R. Dent et al.

Triple-negative breast cancer: clinical features and patterns of recurrence

Clin Cancer Res

(2007)

M. Smid et al.

Subtypes of breast cancer show preferential site of relapse

Cancer Res

(2008)

A. Ring et al.

The treatment of early breast cancer in women over the age of 70

Br J Cancer

(2011)

R. Konigsberg et al.

Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients

Acta Oncol

(2011)

Cited by (25)

An enhanced and efficient approach for feature selection for chronic human disease prediction: A breast cancer study
2024, Heliyon
Computer-aided diagnosis (CAD) systems play a vital role in modern research by effectively minimizing both time and costs. These systems support healthcare professionals like radiologists in their decision-making process by efficiently detecting abnormalities as well as offering accurate and dependable information. These systems heavily depend on the efficient selection of features to accurately categorize high-dimensional biological data. These features can subsequently assist in the diagnosis of related medical conditions. The task of identifying patterns in biomedical data can be quite challenging due to the presence of numerous irrelevant or redundant features. Therefore, it is crucial to propose and then utilize a feature selection (FS) process in order to eliminate these features. The primary goal of FS approaches is to improve the accuracy of classification by eliminating features that are irrelevant or less informative. The FS phase plays a critical role in attaining optimal results in machine learning (ML)-driven CAD systems. The effectiveness of ML models can be significantly enhanced by incorporating efficient features during the training phase. This empirical study presents a methodology for the classification of biomedical data using the FS technique. The proposed approach incorporates three soft computing-based optimization algorithms, namely Teaching Learning-Based Optimization (TLBO), Elephant Herding Optimization (EHO), and a proposed hybrid algorithm of these two. These algorithms were previously employed; however, their effectiveness in addressing FS issues in predicting human diseases has not been investigated. The following evaluation focuses on the categorization of benign and malignant tumours using the publicly available Wisconsin Diagnostic Breast Cancer (WDBC) benchmark dataset. The five-fold cross-validation technique is employed to mitigate the risk of over-fitting. The evaluation of the proposed approach's proficiency is determined based on several metrics, including sensitivity, specificity, precision, accuracy, area under the receiver-operating characteristic curve (AUC), and F1-score. The best value of accuracy computed through the suggested approach is 97.96%. The proposed clinical decision support system demonstrates a highly favourable classification performance outcome, making it a valuable tool for medical practitioners to utilize as a secondary opinion and reducing the overburden of expert medical practitioners.
Addition of chemotherapy to local therapy in women aged 70 years or older with triple-negative breast cancer: a propensity-matched analysis
2020, The Lancet Oncology
Citation Excerpt :
Treatment of older patients with breast cancer is complicated by questions about assessment of functional status, comorbidities, life expectancy, and expected tolerance. Older patients with breast cancer are less likely to receive chemotherapy, although the use of chemotherapy in this population has been increasing since the 2000s.5–8 Comorbidities play an important role in both treatment received and outcomes for older patients with cancer.9
There is a scarcity of data exploring the benefits of adjuvant or neoadjuvant chemotherapy in the treatment of breast cancer in older women. We aimed to explore the effect of adding chemotherapy to local therapy on overall survival in older women with triple-negative breast cancer.
For this propensity-matched analysis, we used data from the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. We included data from women aged 70 years or older with surgically treated, American Joint Committee on Cancer (AJCC) Stage I–III invasive triple-negative breast cancer diagnosed from 2004 to 2014. Patients with T1aN0M0 disease and those with incomplete data on oestrogen receptor status, progesterone receptor status, or HER2 status were excluded. To reduce bias, patients were subdivided into three groups: those who were recommended chemotherapy but did not receive it; those who received chemotherapy; and those for whom chemotherapy was not recommended and not given. The primary outcome was overall survival. Multivariate Cox regression analysis and propensity score matching were done to minimise bias.
Between Jan 1, 2004, and Dec, 31, 2014, 16 062 women with triple-negative breast cancer in the database met the inclusion criteria for this analysis. Median follow-up was 38·3 months (IQR 20·7–46·1, range 0–138·0; 95% CI 37·8–38·7). Collectively, the 5-year overall survival estimate of the 16 062 patients in the study cohort was 62·3% (95% CI 59·7–64·4). 5-year estimated overall survival was 68·5% (95% CI 66·4–70·6) for patients receiving chemotherapy, 61·1% (59·0–63·2) for patients recommended but not given chemotherapy, and 53·7% (51·8–55·8) for patients not recommended chemotherapy and not given chemotherapy (pooled log rank p<0·0001). Multivariate Cox regression analysis of a propensity score-matched sample comparing those who received chemotherapy with those who were recommended but not given chemotherapy (n=1884 matched pairs) identified improved overall survival with chemotherapy (hazard ratio [HR] 0·69 [95% CI 0·60–0·80]; p<0·0001). After stratifying the propensity score matching sample, this benefit persisted for node-negative women (HR 0·80 [95% CI 0·66–0·97]; p=0·007), node-positive women (0·76 [0·64–0·91]; p=0·006), and those with a comorbidity score greater than 0 (HR 0·74 [95% CI 0·59–0·94]; p=0·013).
These data support consideration of chemotherapy in the treatment of women aged 70 years or older with triple-negative breast cancer.
None.
Know your enemy: Genetics, aging, exposomic and inflammation in the war against triple negative breast cancer
2020, Seminars in Cancer Biology
Citation Excerpt :
These disorders have been directly associated with TNBC risk for women during their whole life. Irrespectively of age, it has also to be always kept in mind that therapeutic approaches may trigger cell aging, potentially fueling the vicious circle cancer-inflammation-aging [24,25]. Telomeres are nucleoprotein structures that protect chromosome ends from degradation and recombination.
Triple negative breast cancer (TNBC) is one of the most biologically aggressive and very often lethal breast disease. It is one of the most puzzling women malignancies, and it currently appears not to be a good candidate to a standardized, unanimously accepted and sufficiently active therapeutic strategy. Fast proliferating and poorly differentiated, it is histopathologically heterogeneous, and even more ambiguous at the molecular level, offering few recurrent actionable targets to the clinicians. It is a formidable and vicious enemy that requires a huge investigational effort to find its vital weak spots. Here, we provide a broad review of “old but gold” biological aspects that taken together may help in finding new TNBC management strategies. A better and updated knowledge of the origins, war-like tactics, refueling mechanisms and escape routes of TNBC, will help in moving the decisive steps towards its final defeat.
Alarming Burden of Triple-Negative Breast Cancer in India
2018, Clinical Breast Cancer
Citation Excerpt :
Moreover, it has evolved as an alarming cause of death from cancer in less developed countries.12 It is a heterogeneous disease of different biologic subtypes and are known to possess various clinicopathologic and molecular features with prognostic (eg, tumor size, tumor grade, number of axillary lymph nodes with metastasis) and predictive (eg, estrogen receptor [ER] and progesterone receptor [PR] expression, overexpression of human epidermal growth factor receptor 2 [HER2] proteins) inferences.5,13-15 Using the gene expression profile, breast cancer has been classified into 5 different groups.
Breast cancer is the most prevalent cancer among women worldwide. Among the different breast cancer subtypes, triple-negative breast cancer (TNBC), which is more prevalent among younger age women, is the most aggressive form. Numerous clinicopathologic studies performed throughout the world strongly support the utterly poor prognoses and high recurrence rate of TNBC. The present report details a thorough data survey from Google and PubMed on the burden of TNBC worldwide and other associated factors, with special emphasis on its ever increasing incidence among Indian women. Our analysis revealed that the proportion of TNBC ranges from 6.7% to 27.9% in different countries, with the highest reported percentage in India among all, followed by Indonesia, Algeria, and Pakistan. Most of the other countries (Netherlands, Italy, London, Germany) had a TNBC incidence less than the mean level (ie, 15%). The high incidence of TNBC in the Indian population is associated with vivid risk factors, which primarily include lifestyle, deprivation status, obesity, family history, high mitotic indexes, and BRCA1 mutations. The treatment of TNBC is greatly hampered due to the lack of targeted therapies. Hence, it requires earnest attention towards extensive research for the prevention and development of treatment modalities with high efficacy.
Operation with less adjuvant therapy for elderly breast cancer
2016, Journal of Surgical Research
Citation Excerpt :
The authors of these studies suggested that age alone should not be a contraindication for chemotherapy because older women had similar reductions in survival and recurrence as younger patients. Furthermore, triple negative breast cancer of elderly patients is an aggressive breast cancer subtype claiming as much attention as in younger patients, thus warranting chemotherapeutic intervention irrespective of age.38 For nonluminal breast cancer patients, oral 5FU or CMF may be considered as one of the choices for elderly patients.39,40
The standard of care for elderly women with breast cancer remains controversial. The aim of this study was to clarify the management of elderly breast cancer patients who undergo surgery.
This retrospective single-center cohort study included 2276 breast cancer patients who underwent surgery between 1993 and 2014. The patients were divided into three groups according to age: ≤64 y (young), 65-74 y (older), and ≥75 y (elderly).
The elderly had more advanced stage disease at diagnosis (stage III and IV, 16.2%, 17.5%, and 22.1% for the young, older, and elderly groups, respectively). The elderly were more likely to undergo mastectomy (43.3%, 41.4%, and 50.7%, respectively), omit axillary operation (0.6%, 1.1%, and 9.3%, respectively), and skip radiotherapy after breast-conserving surgery (93.1%, 86.8%, and 29.1%, respectively). Endocrine therapy was widely used in all the groups (94.4%, 93.8%, and 90.1%, respectively), but frequency of chemotherapy was lower in the elderly regardless of hormone receptor (HR) status (40.8%, 25.5%, and 9.3% in HR(+), 87.2%, 75.3%, and 39.5% in HR(−), respectively). Although the locoregional recurrence rate was higher in the elderly (4.2%, 3.4%, and 7.0% at 5 y, respectively; P = 0.028), there were no differences among groups in distant metastasis–free survival or breast cancer–specific survival.
Although elderly patients had more advanced stages of cancer and received less treatment, there were no differences in survival. Omission of axillary dissection, radiation, and chemotherapy after operation may be an option for breast cancer patients aged ≥75 y.
Triple-negative breast cancer and the need for new therapeutic targets
2013, American Journal of Pathology
Citation Excerpt :
With extended observation time after diagnosis the curves cross, leading to a higher risk of breast cancer death in luminal tumors.8,23 Although most TNBCs are found in younger women, approximately 25% of the TN patients are ≥65 years, and because older patients are less likely to receive systemic treatment, this represents a subset of patients with aggressive disease and poor outcome.24 It is known that African American women have a higher mortality rate from breast cancer, which potentially is explained by the higher incidence of TNBC.25
Triple-negative breast cancers (TNBCs) are a diverse and heterogeneous group of tumors that by definition lack estrogen and progesterone receptors and amplification of the HER2 gene. The majority of the tumors classified as TNBCs are highly malignant, and only a subgroup responds to conventional chemotherapy with a favorable prognosis. Results from decades of research have identified important molecular characteristics that can subdivide this group of breast cancers further. High-throughput molecular analyses including sequencing, pathway analyses, and integrated analyses of alterations at the genomic and transcriptomic levels have improved our understanding of the molecular alterations involved in tumor development and progression. How this knowledge should be used for rational selection of therapy is a challenging task and the subject of numerous ongoing research programs. This review summarizes the current knowledge on the clinical characteristics and molecular alterations of TNBCs. Currently used conventional therapeutic strategies and targeted therapy studies are discussed, with references to recently published results on the molecular characterization of TNBCs.

View all citing articles on Scopus

^f: These authors contributed equally to this work.

View full text

Tumor characteristics and recurrence patterns in triple negative breast cancer: A comparison between younger (<65) and elderly (⩾65) patients

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Demographics and tumor characteristics

Discussion

Role of the funding score

Conflict of interest statement

Acknowledgements

Lancet Oncol

Mod Pathol

Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer

JAMA

Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival

J Clin Oncol

Patterns of use of chemotherapy for breast cancer in older women: findings from Medicare claims data

J Clin Oncol

Adjuvant chemotherapy in older women with early-stage breast cancer

N Engl J Med

Undertreatment strongly decreases prognosis of breast cancer in elderly women

J Clin Oncol

Adjuvant treatment of elderly breast cancer patients

Breast

Coming of age: breast cancer in seniors

Oncologist

Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the arimidex, tamoxifen alone or in combination trial

J Clin Oncol

Tumor characteristics and clinical outcome of elderly women with breast cancer

J Natl Cancer Inst

Recent advances: adjuvant therapy for older women with breast cancer

Cancer J

Brain metastases free survival differs between breast cancer subtypes

Br J Cancer

Triple-negative breast cancer

N Engl J Med

Triple-negative breast cancer: clinical features and patterns of recurrence

Clin Cancer Res

Subtypes of breast cancer show preferential site of relapse

Cancer Res

The treatment of early breast cancer in women over the age of 70

Br J Cancer

Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients

Acta Oncol