Prognostic Analysis of Survival in Small Breast Cancers

doi:10.1016/S1072-7515(98)00076-3

Journal of the American College of Surgeons

Volume 186, Issue 5, May 1998, Pages 562-569

Presented at the American College of Surgeons 83rd Annual Clinical Congress, Chicago, IL, October 1997.

https://doi.org/10.1016/S1072-7515(98)00076-3 Get rights and content

Abstract

Background: Routine axillary dissection in patients with invasive small breast cancer remains controversial. We previously reported a model for predicting nodal involvement in patients with T1a or T1b breast cancer that may guide the practice of selective nodal dissection. The objective of this study was to determine whether the prognosticators that predict nodal metastases also predict survival.

Study Design: This study is a retrospective review of 2,153 women with small invasive breast cancer (≤ 1 cm) diagnosed between January 1984 and December 1995. Cases were identified from a statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center in Massachusetts. The impact on survival of patient age (≤40 versus >40 years), nodal status (positive versus negative), tumor size (T1a versus T1b), and tumor grade (1 versus 2 or 3) were analyzed. Breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and the proportional hazards regression method.

Results: There were 388 patients with tumors 0.5 cm or less (T1a) and 1,765 with tumors 0.6–1.0 cm (T1b). Nodal status was known in 68% of cases (1,461 of 2,153), and tumor grade was recorded in 42% of cases (902 of 2,153). In univariate analysis, age, grade, and nodal status were significant in their association with BCSS. Tumor size did not influence BCSS among patients with small invasive tumors. Women older than 40 years had superior survival compared with younger women (93% versus 78% at 5 years; p = 0.01). Similarly, women with low grade (1) tumors did better than those with higher grade (2 or 3) tumors (98% versus 88% at 5 years; p = 0.03). The 5-year BCSS was 96% versus 78% for node-negative versus node-positive disease, and the 10-year BCSS was 91% versus 62% (p = 0.001). In the multivariate analysis, age and nodal status remained firmly associated with survival, although grade lost its significance.

Conclusions: Small tumor size does not affect survival. Although risk profiles for nodal involvement can be constructed to help guide the practice of selective axillary lymphadenectomy in patients with small invasive breast cancers, these factors cannot serve as a surrogate to nodal status in establishing patient prognosis. Nodal status remains the most powerful determinant of survival in breast cancer patients, even those with very small tumors.

Section snippets

Methods

A retrospective review was performed on data obtained from the Rhode Island computerized tumor registry representing a database that includes nine hospitals, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center in Springfield, MA. There were 9,393 women with breast cancer reported to the Hospital Association of Rhode Island and an additional 2,637 women reported to Baystate Medical Center during the 12-year period from January 1984 to December 1995. Of

Results

Included in this analysis were 2,153 women with T1a and T1b breast cancer. Patient ages ranged from 27 to 99 years with a mean of 64.6 years. Only 5.4% of all small breast cancers were diagnosed in women younger than 40 years of age.

A summary of patient and tumor characteristics is given in Table 1. The percentages listed are based on the total number of cases for which a particular variable was known. The status of the axillary nodes was known in 68% (1,461 of 2,153) of the patients. Although

Discussion

There has been much debate regarding the role of axillary dissection in patients with small invasive breast cancers ≤1 cm in size. Controversy has, in part, been fueled by the increasing demand to perform more conservative surgery for breast cancer in general, as well as a drive to reduce health care costs. It is in this setting that physicians treating women with breast cancer have sought alternatives for the information traditionally gained by performing axillary dissection, and more recently

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Cited by (25)

Axillary staging in women with small invasive breast tumours
2006, European Journal of Surgical Oncology
Citation Excerpt :
Maibenco and colleagues found that T1a tumours of favourable histological type had nodal metastases in only 3.9% of cases.21 They concluded that ALND could safely be avoided in T1a (grade I, tubular, mucinous and papillary) and T1b (tubular and mucinous) tumours whilst others have suggested that axillary dissection can be omitted in all patients over the age of 40 years with grade I tumours and no adverse prognosticators.22 Rivadeneira and colleagues identified a subgroup of older women (>60 years) with small (<0.5 cm) well-differentiated (grade 1) T1a tumours without evidence of lymphovascular invasion.23
To identify a group of women with small breast cancers of favourable histological grade for whom observation alone may be an acceptable approach for management of the axilla.
In a retrospective analysis the incidence of nodal metastases was examined in a group of 355 consecutive patients over 55 years of age who underwent mastectomy or breast conserving surgery. All patients had either grade I (<20 mm) or grade II (<15 mm) oestrogen receptor positive tumours without lymphovascular invasion (LVI). In a related study on 173 clinically node negative patients, the rate of axillary recurrence was assessed in patients with small (<10 mm), non-high grade (I and II), ER-positive invasive ductal carcinomas without LVI. Axillary surgery was either omitted (135 patients) or delayed (38 patients) at the time of wide local excision or mastectomy.
The overall incidence of positive nodes in this good prognostic group of patients was 13% (95% confidence interval 9.5–16.5). When the analysis was confined to grade I (≤20 mm) and grade II (≤10 mm) the overall incidence of nodal metastases was 10%. Rates of axillary recurrence at a median follow up of 49 months were only 1% when axillary surgery was omitted according to patient choice/departmental policy with no cases of uncontrolled axillary recurrence.
The risk:benefit ratio for detection of node positive cases in a selected group of older patients does not justify any form of axillary procedure at the time of primary surgery.
Can the survival difference between breast cancer patients in Denmark and Sweden 1989 and 1994 be explained by patho-anatomical variables? - A population-based study
2004, European Journal of Cancer
Citation Excerpt :
Age at diagnosis affects breast cancer survival adversely [6]. Recognised prognostic adverse patho-anatomical variables for survival include involvement of the axillary lymph nodes [10,11], large tumour size [12], poor differentiation [13] and negative oestrogen-receptor status [14]. Registry-based studies comparing relative survival in the Nordic countries have not considered prognostic variables [5,6].
Analyses of data from cancer registries have shown a 10% unit difference in 5-year relative survival between Danish and Swedish patients with breast cancer. This study investigates the effect of age and patho-anatomic variables on this survival difference. Hospital records were collected for women over 40 years of age diagnosed in 1989 or 1994 in east Denmark and south Sweden; patho-anatomical variables and survival were compared between 2289 Danish and 1715 Swedish women. Tumours were smaller, node-negative axillae more frequent and well-differentiated tumours almost 10% more frequent in Sweden. A superior 5-year relative survival in Sweden was found in the 50- to 79-year age group. The adjusted hazard rate ratio between countries was 1.7 in 1989 and 1.3 in 1994. Conditional survival after surviving the first 5 years was similar for the two countries. Adjusting for patho-anatomical variables reduced but did not eliminate the higher risk of death among the Danish patients. Higher population death rates could explain some but not all of the residual elevated risk for Danish women.
Management of T1a breast cancer
2004, Clinical Breast Cancer
Identification of early-stage breast cancers has increased over the past 2 decades primarily because of mammographic screening. The general guidelines to management of breast cancer may not apply to the smallest of these tumors, as their metastatic potential may be smaller than larger tumors. Tumors < 5 mm (T1a) carry an excellent prognosis, despite a variety of treatment approaches. However, some patients' cancer returns. There appear to be some histologic features that can predict a higher risk of axillary metastases, and therefore, a higher risk of distant metastases. Controversy exists over the extent of treatment, as to whether less than conventional treatment, such as mastectomy, axillary evaluation, and breast-conserving surgery and radiation, can be done. T1a lesions associated with extensive ductal carcinoma in situ and T1a lesions in young patients should be treated with caution if less than conventional breast treatment is to be considered. In older patients with good histologic features, axillary assessment may not be necessary. Very wide excision alone may be appropriate for some patients, but partial breast irradiation is under study and may provide a reasonable compromise. Systemic therapy for node-negative patients is not recommended. Recurrences within the breast occur later in early-stage breast cancers than with extensive-stage breast cancers, requiring annual imaging and evaluation for many years.
A model for predicting axillary node metastases based on 2000 sentinel node procedures and tumour position
2002, European Journal of Surgical Oncology
Aims: The purpose was to identify the independent predictive factors of axillary lymph-node metastases (ALNM) in infiltrating ductal carcinoma (IFDC) and to create a prospective, validated statistical model to predict the likelihood of ALNM in patients in the present era of sentinel lymph-node (SLN) biopsy and enhanced histopathology.
Methods: Univariate and multivariate analyses of 13 clinicopathological variables (including tumour location) were performed to determine predictors of ALNM in 1659 eligible SLN biopsy procedures. A logistic regression model was developed and then prospectively validated on a second population of 187 subsequent consecutive procedures.
Results: Age, pathological tumour size, palpability, lymphovascular invasion (LVI), histological grade, nuclear grade, ductal histological subtype, tumour location (quadrant) and multifocality were associated with ALNM in univariate analyses (P < 0.001). Of these, only palpability and histological grade were not statistically associated with ALNM in the multivariate analysis (P> 0.05). The frequency of ALNM in upper-inner-quadrant (UIQ) tumours was 20.6%, compared with 33.2% for all other quadrants (P<0.0005). There was no statistical difference between UIQ and other-quadrant tumours in any clinicopathological variables analysed. The logistic regression model, developed based on the population of 1659, had the same accuracy, sensitivity, specificity, positive predictive value and negative predictive value when applied prospectively to the second population.
Conclusion: Tumour size, LVI, age, nuclear grade, histological subtype, multifocality and location in the breast were independent predictive factors for ALNM in IFDC. ALNM is less frequent in UIQ tumours than in other-quadrant tumours. Our prospectively validated predictive model could be valuable in pre-operative patient discussions, although staging of the axilla in the individual patient remains necessary.
Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: Analysis in more than 900 patients
2000, Journal of the American College of Surgeons
Background: Axillary lymph node metastasis (ALNM) represents the single most important prognostic indicator in patients diagnosed with breast cancer. The proportion of ≤ 1-cm (T1a, T1b) invasive breast carcinomas is increasing. The incidence and predictive factors associated with ALNM in patients with ≤ 1-cm tumors remains unclear and the role of axillary lymph node dissection in these patients has been questioned. The purpose of this study was to determine clinical and pathologic factors predictive of ALNM in patients with ≤ 1-cm invasive breast carcinomas by univariate and multivariate analyses.
Study Design: Review analysis from a prospective database identified patients with ≤ 1-cm invasive breast cancers treated at our institution between 1990 and 1996. All patients underwent a resection of the primary tumor and axillary lymph node dissections. Routine patient and tumor characteristics evaluated included: age, race, tumor size, histologic grade, estrogen and progesterone receptor status, and lymphatic and vascular invasion. Univariate and multivariate analyses were performed. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are presented.
Results: A total of 919 patients were identified in this study with tumors ≤ 1 cm. These included 199 patients (21.7%) with T1a tumors and 720 patients (78.3%) with T1b tumors. ALNM was detected in 165 patients with an overall incidence of 18.0%. Of the ALNM group, 32 patients (19.4%) had T1a tumors and 133 patients (80.6%) had T1b tumors. Four variables were found to be significant in univariate analysis. These included: increasing tumor size, poor histologic grade, presence of lymphatic or vascular invasion, and younger age of the patient. An increase in tumor size was associated with a significant risk of ALNM (OR = 2.66, 95% CI = 1.28 to 5.75; p = 0.01). Poor tumor grade and the presence of lymphatic or vascular invasion were also associated with an increased risk of ALNM (OR = 2.69, p = 0.003 and OR = 5.52, p = 0.0001, respectively). Patients with ALNM were more likely to have a tumor grade of 3 (25.0% ALNM versus 12.5% node-negative, p = 0.004) and lymphatic or vascular invasion (16.9% ALNM versus 3.5% node-negative, p < 0.0001). In multivariate analysis, an increased risk of ALNM was demonstrated with increasing tumor size (0.1-cm increments), poor histologic grade, and younger age.
Conclusions: This study investigated clinical and pathologic factors influencing ALNM in patients with T1a and T1b breast carcinomas. We have identified three factors by multivariate analysis as significant independent predictors of ALNM in this group of patients. These include increasing tumor size, poor histologic grade, and younger age. Given the significant amount of ALNM demonstrated in this study (overall 18%) and the inability to identify a subgroup of patients that had an acceptable low risk of ALNM, the complete omission of assessing the axilla for metastatic disease in patients with small breast cancers cannot be advocated. Our recommendation for patients diagnosed with T1a and T1b tumors is to have their axilla investigated for metastatic disease either by traditional axillary lymph node dissections or by intraoperative lymphatic mapping and sentinel lymph node biopsy techniques.
Axillary dissection
2000, Operative Techniques in General Surgery
Axillary dissection remains an important aspect of breast cancer treatment. No other factor has been demonstrated to be of more prognostic significance in breast cancer than the presence or absence of axillary metastases.^12–14 An axillary sampling that excises fewer than 6 nodes is inadequate for staging and should not be substituted for a complete axillary dissection. Note that directed sentinel node biopsy is different than random axillary lymph node sampling, and these 2 procedures should not be confused. Generally, the pathologist will identify and examine some 15 to 25 nodes in an axillary dissection specimen. The absolute number of axillary nodes varies from individual to individual and with the diligence of pathological examination. Recently, it has been our practice to process the axillary nodes for permanent sections, allowing multiple levels of each node to be studied. Cytokeratin staining is also used selectively.
As axillary dissection enters its third century, it must continue to provide complete staging information, combined with preservation of function and cosmetic acceptance. The impact of sentinel lymph node biopsy on axillary dissection is currently being defined.¹⁵ However, it is clear that precise, reliable axillary staging information will remain an indispensable part of surgery for primary breast cancer.^16,17

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Original Scientific ArticlesPrognostic Analysis of Survival in Small Breast Cancers

Abstract

Section snippets

Methods

Results

Discussion

Eur J Cancer

The impact of histopathology on nodal metastases in minimal breast cancer

Arch Surg

Treatment of early stage breast cancer

JAMA

How to use prognostic factors in axillary node-negative breast cancer patients

J Natl Cancer Inst

Treatment decisions in axillary node- negative breast cancer patients

J Natl Cancer Inst Monogr

Original Scientific Articles
Prognostic Analysis of Survival in Small Breast Cancers