Natural history of node-negative breast cancer: are conventional prognostic factors predictors of time to relapse?

doi:10.1054/brst.2002.0462

The Breast

Volume 11, Issue 5, October 2002, Pages 442-448

https://doi.org/10.1054/brst.2002.0462 Get rights and content

Abstract

The purpose of this study was to determine a subpopulation of node-negative breast cancer patients at high risk of metastases and to analyse the relationship between conventional prognostic factors and the onset of metastatic disease. Patients with node-negative breast cancer, who were not receiving systemic adjuvant therapy, were prospectively enrolled into a multicentre study. We studied the onset of metastatic disease in relation to family history, age, and tumour characteristics of 2683 registered patients, 2213 were available for analysis. Median follow-up was 100 months. Metastatic disease-free survival was 88% at 5 years and 80% at 10 years. The two strongest prognostic factors in a multivariate analysis tumour Scraff, Bloom and Richardson (SBR) grade (P<0.0001) and size (P<0.02), were used to classify patients into three groups with different risks of relapse at 10 years: (1) lowest (8.4%) risk: SBR I and ≤1 cm; (2) intermediate (20%) risk: SBR I and >1 cm or SBR II or SBR III and ≤2 cm; (3) highest (32%) risk: SBR II or SBR III and >2 cm. A peak in the incidence of metastases was noted between 2 and 4 years, and a nadir between 6 and 8 years, after surgery. SBR grade is a highly predictive factor in node-negative breast cancer. The time course of the appearance of metastases is not linear. Prognostic factors are related to the height of an early peak in the occurrence of metastases rather than to the timing of this peak.

References (39)

A De La Rochefordière et al.
Age as prognostic factor in premenopausal breast carcinoma
Lancet
(1993)
M Baum et al.
Does breast cancer exist in a state of chaos?
Eur J Cancer
(1999)
R Heimann et al.
Angiogenesis and estrogen receptor in young women with breast cancer
Int Radiat Oncol Biol Phys
(1997)
HF Rauschecker et al.
Eight-year results of a prospective non-randomized study on therapy of small breast cancer. The German Breast Cancer Study Group (GBSG)
Eur J Cancer
(1998)
A Goldhirsch et al.
Fifth International Conference on Adjuvant Therapy of Breast Cancer, St Gallen, March 1995. International Consensus Panel on the Treatment of Primary Breast Cancer
Eur J Cancer
(1995)
JF Stewart et al.
Oestrogen receptors, sites of metastatic disease and survival in recurrent breast cancer
Eur J Cancer
(1981)
CL Carter et al.
Relation of tumour size, lymph node status, and survival in 24,740 breast cancer cases
Cancer
(1989)
PP Rosen et al.
Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up
J Clin Oncol
(1993)
PP Rosen et al.
Pathological prognostic factors in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma: a study of 644 patients with median follow-up of 18 years
J Clin Oncol
(1989)
HJG Bloom et al.
Histological grading and prognostic in breast cancer: a study of 1409 cases of which 359 followed for 15 years
Br J Cancer
(1957)

B Fisher et al.

Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicator of prognosis in node negative breast cancer patients: findings from National Surgical adjuvant Breast and Bowel Project Protocol B-06

J Clin Oncol

(1988)

HO Adami et al.

Age at first primary as a determinant of the incidence of bilateral breast cancer. Cumulative and relative risks in a population based case-control study

Cancer

(1985)

BL Fowble et al.

The influence of young age on outcome in early stage breast cancer

Int J Radiat Oncol Biol Phys

(1994)

TG Karrison et al.

Dormancy of mammary carcinoma after mastectomy

JNCI

(1999)

P Valagussa et al.

Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients

Cancer

(1978)

F Rank et al.

Histologic malignancy grading of invasive ductal breast carcinoma. A regression analysis of prognostic factors in low-risk carcinomas from a multicenter trial

Cancer

(1987)

F Clayton

Pathological correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor

Cancer

(1991)

V Le Doussal et al.

Nuclear characteristics as indicators of prognosis in node negative breast cancer patients

Breast Cancer Res Treat

(1989)

RA Huseby et al.

Node-negative breast cancer treated by modified radical mastectomy without adjuvant therapies: variables associated with disease recurrence and survivorship

J Clin Oncol

(1988)

Cited by (20)

Metastasis-free interval in breast cancer patients: Thirty-year trends and time dependency of prognostic factors. A retrospective analysis based on a single institution experience
2018, Breast
Citation Excerpt :
Among all the variables characterizing node disease, only LNR appeared as a strong independent prognostic factor in our multivariate analysis [6]. Previous studies have already established that positive lymph nodes represent the most important prognostic factor of survival in breast cancer patients and that the worse outcome is directly correlated with the number of positive lymph nodes [30–32]. Even if the number of positive lymph nodes is significant, whenever LNR is also introduced in the model, it is only the LNR that appears as a strong independent prognostic factor [33].
Breast cancer remains the leading cause of cancer death in French women in spite of continuously improving management. The objectives of this study were to analyse trends in the metastasis-free interval over the past 30 years and to identify the prognostic factors of survival, while accounting for time dependency.
A total of 1613 patients diagnosed with invasive non-metastatic breast cancer at Saint Vincent de Paul Hospital, Lille, France between 1977 and 2013, were followed for outcome (metastasis-free interval). Cohort entry time delay, a continuous temporal covariate, was defined to assess improvement of outcome. Data were analysed using the Cox proportional hazards model and presented as hazard ratio (HR).
Metastatic disease developed during follow-up in 446 (27.6%) patients. Cohort entry time delay exhibited strong independent prognostic value while accounting for multiple prognostic factors including: tumour size (HR = 1.62, 95 %CI 1.37–1.91); rapid tumour growth (HR = 1.59, 95%CI 1.17–2.16); lymph node ratio (HR = 2.29, 95%CI 1.97–2.66); histological grade (grade 2 was significant only during the first 10 years after diagnosis, grade 3 and progesterone receptor status only during the first 5 years after diagnosis); and oestrogen receptor status (significant only during the first 8 years (HR = 0.75, 95%CI 0.58–0.96)).
The current study showed an improvement in the prognosis of breast cancer patients over the past 30 years and pointed to the importance of evaluating covariates with time-varying effects.
Quantitative apparent diffusion coefficient measurement obtained by 3.0 Tesla MRI as a potential noninvasive marker of tumor aggressiveness in breast cancer
2016, European Journal of Radiology
Citation Excerpt :
In LN negative patients, the presence of lymphovascular invasion (LVI) has been reported to adversely impact prognosis because patients with positive LVI had a higher rate of distant metastases, increased local recurrence rate after breast conservation therapy and a higher mortality rate [5,11]. Studies have also reported LVI as a possible independent prognostic factor [12,13]. However, due to limited sampling, preoperative assessment of LVI status of a tumor by core-biopsy is difficult.
To assess the association between apparent diffusion coefficient (ADC), and histological prognostic parameters in malignant breast lesions. The ability of ADC to identify lesions with the presence of Lymphovascular invasion (LVI) in breast carcinoma was also examined.
This HIPAA-compliant retrospective study consisted of 212 consecutive patients with known cancers who underwent 3.0 T MRI between January 2011 and 2013. In this study, a total of 126 malignant lesions in 114 women, who had undergone DWI (b-values of 0 and 1000 s/mm²) in addition to diagnostic MRI, were included. Patients with less than 0.8 cm lesions, or those who underwent neoadjuvant chemotherapy or suboptimal DW images were excluded. Classical prognostic factors [lesion size, histopathological type and grade, lymph node (LN) status and lymphovascular invasion (LVI)], molecular prognostic markers [estrogen receptor (ER), progesterone receptor (PR) and human epidermal grow factor receptor 2 (HER2)] were reviewed and recorded. A region of interest (ROI) was drawn within the lesions to measure ADC values. Statistical analyses were performed by the Wilcoxon rank sum test (statistical significance at P < 0.05). Adjusted p values from multiple comparison analysis were also calculated.
This study demonstrates an inverse correlation between ADC and LVI in malignant lesions and the ability of ADC to identify aggressiveness in lesions with positive LVI. Tumor size, grade, ER, PR, HER2 and lymph node status did not impact tumor ADC value. However, tumors with LVI showed significantly lower ADC values when compared to tumors without LVI, regardless of the enhancement type, histological grade, histological type, and LN status.
Our study shows that ADC could be a potential clinical adjunct in the evaluation of prognostic factors related to malignant lesion aggressiveness such as LVI.
UPA/PAI-1, Oncotype DXTM, MammaPrint®. Prognosis and predictive values for clinical utility in breast cancer management
2015, Bulletin du Cancer
Clinical data analysis using artificial neural networks (ANN) and principal component analysis (PCA) of patients with breast cancer after mastectomy
2007, Reports of Practical Oncology and Radiotherapy
Exploitation of the several types of information on patient, disease and treatment variables ranging from sociological to genetic ones by means of chemometric analysis was considered and evaluated.
Performance of modern data processing methods, namely principal component analysis (PCA) and artificial neural network (ANN) analysis, is demonstrated for predictions of the recurrence of breast cancer in patients treated previously with mastectomy.
The data on 718 patients were retrospectively evaluated. 11 subject and treatment variables were determined for each patient. A matrix of 718×11 data points was subjected to PCA and ANN processing. The properly trained ANN was used to predict the patients with recurrence and without recurrence within a 10-year period after mastectomy.
It was found that the prognostic potency of the trained and validated ANN was reasonably high. Additionally, using the principal component analysis (PCA) method two principal components, PC1 and PC2, were extracted from the input data. They accounted cumulatively for 37.5% of the variance of the data analyzed. An apparent clustering of the variables and patients was observed – these have been interpreted in terms of their similarities and dissimilarities.
It has been concluded that ANN analysis offers a promising implementation to established methods of statistical analysis of multivariable data on cancer patients. On the other hand, PCA has been recommended as an alternative to classical regression analysis of multivariable clinical data. By means of ANN and PCA practically useful systematic information may be extracted from large sets of data, which can be of value for prognosis and appropriate adjustment of the treatment of breast cancer.
Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma
2006, European Journal of Cancer
This study aimed to test the hypothesis that lymphovascular invasion adds prognostic information to histological grade and tumour size in node-negative invasive carcinoma of the breast. Lymphovascular invasion was assessed in haematoxylin and eosin tumour sections from 2760 patients with node-negative invasive breast carcinoma treated with definitive surgery. Patients were divided into two groups: 990 in the no adjuvant therapy series (diagnosed in 1974–1988) with median follow-up of 13 years; and 1765 in the selective adjuvant therapy series (1988–2000) with median follow-up of 6.8 years. Lymphovascular invasion was identified in 19% of tumours and was associated with larger tumour size, higher histological grade and younger age. Overall, survival was associated on multivariate analysis with lymphovascular invasion, histological grade and tumour size in both patient series, and with histological type in the no adjuvant therapy series. In conclusion, lymphovascular invasion is an independent prognostic factor in node-negative breast cancer and should be considered in decisions about adjuvant treatment in this group of women.
Minimal and small size invasive breast cancer with no axillary lymph node involvement: The need for tailored adjuvant therapies
2004, Annals of Oncology
Citation Excerpt :
Controversy regarding the clinical algorithm for patients with small tumors is related to the limited information available on their prognosis [17]. Studies published reported a long-term DFS ranging between 79% and 98% [18–21]. Factors related to good prognosis were low grade [19, 20], old age [21, 22] and ER-negative disease [18, 21].
Prognosis of patients with node-negative disease and tumor size <1 cm is a matter of controversy. While data exist to clearly correlate small tumor size to better prognosis, the fact that very small breast cancers may express biological markers of dire prognosis leads many to ignore small tumor size during treatment decision-making.
Data from 425 patients classified as having node-negative pT1mic, pT1a or pT1b after surgery (from April 1997 to December 2001) at the European Institute of Oncology, were analyzed to be described as disease-free according to prognostic variables including: Ki-67 (<20% versus ≥20% of the cells), ER (absent versus positive ≥1% of the cells), PgR (absent versus positive ≥1% of the cells), grade, overexpression or amplification of HER2/neu, presence of peritumoral vascular invasion and age (by decade). The median follow-up for this cohort of patients was 43 months.
No local or distant relapse was observed for patients with pT1mic breast cancer; 4-year disease-free survival for pT1a and pT1b was 97.0% and 97.6%, respectively. In both univariate and multivariate analyses the most relevant prognostic factor for this low-risk population was Ki-67 labeling. The 4-year disease-free survival was 99.2% for tumors with low Ki-67 and 93.3% for tumors with high Ki-67 (≥20%) labeling. The hazard ratio (HR) for patients with high Ki-67 was 12.9 (95% CI 1.5–112.0, P=0.02).
Within the first 4 years, microinvasive breast cancer parallels ductal carcinoma in situ (DCIS) rather than invasive carcinoma. Costs and benefits of adjuvant therapy should be accurately weighted in these patients. Patients with pT1a and pT1b, node-negative disease have a limited but substantial risk of recurrence and therefore adjuvant therapy, according to endocrine responsiveness of the tumor and patient preference, should continue to be offered as a reasonable treatment option.

View all citing articles on Scopus

^f1: Address correspondence to: Dr Thierry Delozier, Service de Radiotherapie, Centre François Baclesse, Route de Lion/mer, B.P. 5026, F-14076 CAEN Cedex 5, France. Tel.: +33 231 45 50 50; Fax: +33 231 45 50 57; E-mail: [email protected]

View full text

Original ArticleNatural history of node-negative breast cancer: are conventional prognostic factors predictors of time to relapse?

Abstract

Lancet

Eur J Cancer

Int Radiat Oncol Biol Phys

Eur J Cancer

Eur J Cancer

Eur J Cancer

Relation of tumour size, lymph node status, and survival in 24,740 breast cancer cases

Cancer

Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up

J Clin Oncol

Pathological prognostic factors in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma: a study of 644 patients with median follow-up of 18 years

J Clin Oncol

Histological grading and prognostic in breast cancer: a study of 1409 cases of which 359 followed for 15 years

Br J Cancer

Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicator of prognosis in node negative breast cancer patients: findings from National Surgical adjuvant Breast and Bowel Project Protocol B-06

J Clin Oncol

Age at first primary as a determinant of the incidence of bilateral breast cancer. Cumulative and relative risks in a population based case-control study

Cancer

The influence of young age on outcome in early stage breast cancer

Int J Radiat Oncol Biol Phys

Dormancy of mammary carcinoma after mastectomy

JNCI

Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients

Cancer

Histologic malignancy grading of invasive ductal breast carcinoma. A regression analysis of prognostic factors in low-risk carcinomas from a multicenter trial

Cancer

Pathological correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor

Cancer

Nuclear characteristics as indicators of prognosis in node negative breast cancer patients

Breast Cancer Res Treat

Node-negative breast cancer treated by modified radical mastectomy without adjuvant therapies: variables associated with disease recurrence and survivorship

J Clin Oncol

Original Article
Natural history of node-negative breast cancer: are conventional prognostic factors predictors of time to relapse?