Tumour size as a predictor of axillary node metastases in patients with breast cancer

BACKGROUND: The ability to predict the behaviour of breast cancer from its dimensions allows the clinician to inform a woman about the absolute benefits of adjuvant therapies or further surgery to control her disease. Tumour size and grade are independent predictors of nodal disease. This study aims to generate a tool, using Australian data, allowing surgeons to calculate the probability of axillary lymph node involvement in a preoperative setting. METHODS: The histological reports of patients with breast cancer treated in 1995 in New South Wales were examined and tumour size, grade and nodal status recorded. Univariate and multivariate analyses identified predictors of node positivity and, using linear regression analysis, a simple formula to predict nodal involvement was derived. RESULTS: In a 6-month period, 754 women had non-metastatic, unifocal breast cancer treated with surgery and complete axillary dissection and 283 (37.5%) had positive nodes. Tumour size remained an independent predictor of node positivity and the probability (%), y, of nodal involvement may be predicted by the formula y = 1.5 x tumour size (mm) + 7, r = 0.939 and P = 0.001. CONCLUSIONS: This paper shows the need to assess the axilla in every patient because even patients with small tumours (0-5 mm) have the possibility of axillary involvement (7-14.5%). Use of this simple formula allows clinicians and patients to make informed decisions about the possible need for a full axillary dissection to reduce the chance of understaging and potentially undertreating a woman's breast cancer.     

Predictors for extensive nodal involvement in breast cancer patients with axillary lymph node metastases

PurposeVarious prediction models have been developed to predict the risk of having no additional axillary metastases in patients with a positive sentinel lymph node biopsy (SLNB), thereby disregarding patients with a positive ultrasound-guided lymph node biopsy (UGLNB). However, in the post-Z0011 trial era it is important to identify all patients with extensive nodal involvement for whom axillary treatment might still be beneficial. Therefore, the aim of this study is to identify factors predicting extensive nodal involvement (≥3 positive nodes) in the axilla, with the emphasis on the method of axillary staging: node positivity by UGLNB versus SLNB.MethodsAll patients diagnosed with invasive breast cancer between January 2006 and December 2011 at the Máxima Medical Center were included. Univariate and multivariate logistic regression analyses were performed.ResultsWe included 302 cases, representing 301 node positive patients, of whom 177 cases had 1 or 2 positive lymph nodes and 125 cases had ≥3 positive lymph nodes. Multivariate analyses showed that a positive UGLNB (OR = 5.10; 95%CI = 2.78–9.36), lymphovascular invasion (OR = 3.60; 95%CI = 1.79–7.23) and a larger tumor size (OR = 1.03 per mm increase; 95%CI = 1.00–1.06) were significantly associated with extensive nodal involvement in patients with invasive breast cancer.ConclusionThis study shows that a positive axilla, determined by UGLNB, is the most important factor for predicting further extensive nodal involvement. Hence, the role of axillary staging by ultrasound should be redefined since it might play an important role in selecting patients who may still benefit from axillary treatment.     

The impact of lymph node metastases on the survival of breast cancer patients with ten or more positive lymph nodes

To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10–15 nodes, or the 11 with 16–25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%–75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with <50% or >75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.     

Frequency and predictors of axillary lymph node metastases in invasive breast cancer

Background: The objectives of the present study were to evaluate the incidence and predictors of axillary lymph node metastases (ALNM) in patients with breast cancer, and to identify if axillary surgery could be safely omitted in selected patients. Methods: Between January 1996 and May 2000, 492 patients underwent 501 axillary lymph node dissections (ALND). The incidence of ALNM was correlated with clinical and pathological characteristics by univariate and multivariate analyses. Results: Axillary lymph node metastases were found in 41% (207/501) of cases. Univariate analysis showed that palpability of primary and axillary lymph node (ALN), pathological tumour size, grade, lymphovascular invasion (LVI) and multifocality or multicentricity were significant predictors of ALNM. By multivariate analysis, palpability of ALN, pathological tumour size, LVI and multifocality or multicentricity remained as independent predictors. Among the 431 cases without palpable ALN, no ALNM were found if the tumour was ≤ 5 mm, non‐multifocal or multicentric, and without LVI, or the tumour was a tubular or mucinous car­cinoma ≤ 15 mm (n = 21). The frequency of ALNM in the absence of the other risk factors was 11% (7/64) if the tumour size was > 5–10 mm, and 17% (19/113) if the tumour was > 10–20 mm. However, the incidence of ALNM was 72% for the 32 clinically node‐negative cases with multifocal or multicentric tumour ≥ 10 mm and LVI. Those patients with palpable ALN (n = 66) had a greater than 50% risk of ALNM. Conclusions: Routine ALND could be omitted in clinically node‐negative patients with either a ≤ 5‐mm, LVI‐negative tumour, or a ≤ 15‐mm tubular or mucinous carcinoma. Axillary lymph node dissection is still useful for determining pathological nodal status in all other cases, and in most cases with palpable ALN, as a therapeutic manoeuvre.     

Preoperative FDG-PET for axillary metastases in patients with breast cancer

HYPOTHESIS: Fludeoxyglucose F 18 (FDG) positron emission tomography (PET) can be used to predict axillary node metastases. DESIGN: Case series. SETTING: Comprehensive breast care center. PATIENTS: Fifty-one women with 54 biopsy-proven invasive breast cancers. INTERVENTION: Whole-body FDG-PET performed before axillary surgery and interpreted blindly. MAIN OUTCOME MEASURES: Axillary FDG activity, quantified by standardized uptake value (SUV); axillary metastases, quantified histologically; and tumor characteristics. RESULTS: There was PET activity in 32 axillae (59%). The SUVs ranged from 0.7 to 11.0. Twenty tumors had an SUV of 2.3 or greater, and 34 had an SUV of less than 2.3. There were no significant differences between these 2 groups except in axillary metastasis size (SUV /=2.3): mean age, 53 vs 58 years (P = .90); mean modified Bloom-Richardson score, 7.7 vs 7.6 (P = .20); lymphovascular invasion present, 25% vs 36% (P = .40); mean Ki-67 level, 25% vs 32% (P = .20); mean tumor size, 2.9 vs 3.2 cm (P = .05); and axillary metastasis size, 0.9 vs 1.7 (P = .001). By adopting an SUV threshold of 2.3, FDG-PET had a sensitivity of 60%, a specificity of 100%, and a positive predictive value of 100%. CONCLUSIONS: Patients with an SUV greater than 2.3 had axillary metastases. This finding obviates the need for sentinel lymph node biopsy or needle biopsy to diagnose axillary involvement. Surgeons can proceed to axillary node dissection to assess the number of nodes involved, eliminate axillary disease, or perhaps provide a survival benefit if preoperative FDG-PET has an SUV greater than 2.3.     

A case of intraductal multicentric breast carcinoma with bilateral axillary metastases

It is recognized that the breast cancer is frequently accompanied by local and regional nodal metastases, but contralateral axillary dissemination is considered a rarity. It is presented a case of a 42 old female patient with intraductal multicentric right mamar carcinoma (T2) with bilateral axillary nodal metastases who had underwent to the complex treatment: surgical, chemotherapy and radiotherapy and hormonal therapy. The prognosis is reserved. It is required a careful supervision from point of view clinical biological, mamography, echography, tomography, RMN for diagnosis of recurrences, metastases and becoming a bilateral cancer at the remaining breast.     

Occult axillary lymph node metastases in breast cancer do matter: results of 10-year survival analysis

Axillary lymph node status is one of the most powerful prognostic factors for patients with breast cancer and is often critical in stratifying patients into adjuvant treatment regimens. In 203 apparently node-negative cases of breast cancer, a combination of immunohistochemical staining and step-sectioning identified occult metastases in 25% of cases. Ten-year follow-up information is available for these patients. Histologic features of the primary tumor and immunohistochemical staining for estrogen receptor, progesterone receptor, Her-2, and p53 were also evaluated. With multivariate analysis, both occult metastases and higher histologic grade of the primary tumor were independent predictors of disease-free survival. Histologic grade was the only significant independent predictor of overall survival. Estrogen receptor, progesterone receptor, Her-2, and p53 status did not predict the presence of metastases or survival when all tumor types were considered together. Metastases >0.5 mm significantly predicted a poorer disease-free survival when invasive ductal carcinomas were considered alone. Histologic grade was significantly associated with disease-free survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients. The presence of occult metastases approached significance for overall survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients.     

Influence of estrogen receptors on survival and recurrence in patients with breast cancer without lymph node metastases

A retrospective chart review was conducted to determine the prognostic effect of estrogen receptor (ER) protein in patients with node-negative operable breast cancer. One hundred nine patients with breast cancer whose tumors underwent ER analysis and whose lymph node negativity was established histologically were studied. Based on life-table analysis, the overall survival at six years was 92.7% for ER-positive patients, 95.3% for ER-negative patients, and 94.4% for ER-borderline patients. The disease-free survival was 83.3%, 92.8%, and 71.4%, respectively. Survival and disease-free survival were also correlated to menopausal status. The difference in survival was not statistically significant at six years. We conclude that in node-negative primary operable breast cancer, ER status should not be used as a discriminant for adjuvant treatment.     

Nonsentinel node metastases in breast cancer patients with isolated tumor cells in the sentinel node: implications for completion axillary node dissection

BACKGROUND: Controversy exists regarding axillary dissection (ALND) for sentinel node (SLN) metastases detected as isolated tumor cells (ITC). We hypothesized that the number of positive non-SLNs is low and ALND is unnecessary for most patients with ITC. METHODS: From 1995 to 1999, 634 breast cancer patients underwent SLND. SLNs were examined using immunohistochemistry if hematoxylin and eosin was negative. ALND was recommended for ITC-positive SLNs. RESULTS: Seventy-eight patients (12.3%) with ITC-positive SLNs were offered ALND. Sixty-one consented, whereas 17 refused. Fifty-eight (95.1%) had negative non-SLNs. Three (4.9%) had non-SLN metastases. One patient (1.6%) had macrometastatic disease, whereas 2 (3.3%) had micrometastases. No ITC-only-positive SLN patient experienced axillary recurrence. CONCLUSIONS: When ALND was performed for ITC, 1.6% of non-SLNs harbored macrometastases and 3.3% had micrometastases. When ALND was not performed, axillary recurrence was not seen. The low risk of non-SLN disease in this study fails to support the routine use of ALND for ITC-positive SLNs.     

Association between extent of axillary lymph node dissection and survival in patients with stage I breast cancer

Background: The role of axillary lymph node dissection for stage I (T1N0) breast cancer remains controversial because patients can receive adjuvant chemotherapy regardless of their nodal status and because its therapeutic benefit is in question. The purpose of this study was to determine whether extent of axillary dissection in patients with T1N0 disease is associated with survival. Methods: Data from 464 patients with T1N0 breast cancer who underwent axillary dissection from 1973 to 1994 were examined retrospectively. Kaplan-Meier estimates of overall survival, disease-free survival, and recurrence were calculated for patients according to the number of lymph nodes removed (<10 or ⩾10; <15 or ⩾15), and survival curves compared using the Wilcoxon-Gehan statistic. Cox proportional hazards regression modelling was used to adjust for confounding prognostic variables. Results: Median follow-up time was 6.4 years. Patient groups were similar in age, menopausal status, tumor size, hormonal receptor status, type of surgery, and adjuvant therapy. There was a statistically significant improvement in disease-free survival in the ⩾10 versus <10 nodal groups (P<.01). Five-year estimates of survival were 75.7% and 86.2% for <10 nodes and ⩾10 nodes, respectively; 10-year estimates were 66.1% and 74.3%. There also was a notable improvement in the survival comparison of patients with <15 versus ⩾15 nodes (P⩽.05). These findings were confirmed in the multivariate analysis. Conclusions: These results may reflect a potential for misclassification of tumor stage among patients who had fewer nodes removed. The data, however, suggest that in patients with Stage I breast cancer, improved survival is associated with a more complete axillary lymph node dissection. Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Factors affecting axillary lymph node metastases in patients with T1 breast carcinoma

The purpose of this study was to determine factors associated with the incidence of axillary lymph node metastases (ALNM) in T1 tumors and cases in which axillary dissection could be omitted. Data from 195 patients with T1 primary invasive breast cancer (size < or = 2 cm) who underwent either mastectomy or wide local excision of the tumor and axillary dissection were reviewed. ALNM was found in 59 of 195 patients with T1 tumors (30.3%). Tumor size was found to be the only independent predictor of ALNM, having a directly analogous relationship with the probability of invaded nodes: T1a (< or = 5 mm) tumors had 0 per cent ALNM, whereas T1b (5 mm < T1b < or = 10 mm) and T1c (10 mm < T1c < or = 20 mm) tumors had 25.7 per cent and 33.8 per cent ALNM respectively. Among the other factors studied (patient age, tumor site, hormone receptor status, histologic type, and grade of the tumor) only the histologic grade of the tumor cells appeared to correlate with the incidence of lymph node involvement, but this was not statistically significant. In conclusion only tumor size has statistically significant correlation with the incidence of ALNM. Routine axillary dissection could be omitted only in patients at minimal risk of ALNM (ductal carcinoma in situ and T1a) and when treatment decisions were not influenced by lymph node status (e.g., elderly patients with clinically negative axilla). Axillary dissection (at least levels I and II) should be performed in all cases with primary invasive breast cancer with tumor size > 5 mm.     

Lymph node imprint cytology for the rapid assessment of axillary node metastases in breast cancer

Lymph node imprint cytology was performed on 86 nodes from 13 consecutive patients with breast cancer undergoing simple mastectomy with axillary node sampling, and a prospective comparison with paraffin section was made. The results showed a diagnostic sensitivity and specificity of 0.93 and 0.98 respectively. The predictive value of a positive result was 0.98. This technique can be used to identify patients with Stage I disease rapidly, thereby allowing their exclusion from treatment with peri-operative chemotherapy.     

Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival

We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance.     

A four node axillary sampling trial on breast cancer patients

The surgical management of axillary lymph nodes in early breast cancer remains controversial, although several maneuvers have been developed such as axillary node clearance (ANC), four node axillary sampling (4NAS), and sentinel node biopsy. A total of 237 cases of primary breast cancer at stages I and II were studied prospectively to elucidate the correlation between 4NAS and ANC. All calculated values by 4NAS showed high sensitivity, specificity, and overall accuracy as follows in this study: 92.9%, 100% and 98.5% for stage I, and 93.8%, 100% and 98.3% for stage II. Likewise, the false negative (FN) rates were 7.1% for stage I, 6.3% for stage II, 6.7% for T1, 6.4% for T2, 7.4% for N0, 0% for N1, and 6.5% for all cases. These rates were very low, although 7.4% for N0 and 0% for N1 were quite clearly different. This implies that all FN cases were N0, and were caused by micrometastases with normal consistency and size. 4NAS may be as accurate a procedure as ANC in assessing axillary nodal stage.     

Occult lymph node metastases in patients with 'node negative' breast carcinoma treated with conservation surgery and axillary node sample and who subsequently developed axillary recurrence

We examined axillary lymph nodes from 26 patients with node-negative breast cancer managed by axillary node sampling and no further axillary treatment, but who subsequently developed axillary recurrence after a mean follow-up of 7 years to determine the incidence of micrometastatic disease in these patients. Twenty-six matched controls with an identical length of follow-up who were node-negative on an axillary node sample, but have not developed axillary recurrence, also underwent node examination and the incidence of metastases in the two groups were compared. Lymph nodes were sectioned at two additional levels 100 microm apart. Sections at each level were stained with haematoxylin and eosin (H&E) and antibodies to PanCK and MUC1 protein. The original H&E section from each node was reviewed and additional sections from each lymph node were examined by a pathologist who was blinded to outcome. Review of the original H&E sections of the nodes revealed metastases that had been overlooked at the time of diagnosis in two (8%) patients from the recurrence group. A further two (8%) patients from the recurrence group and three (12%) from the control group had axillary nodes which contained micrometastases. Immunocytochemistry was important in identifying all micrometastases. There was no significant difference in the incidence of axillary node micrometastases between patients with and without axillary node recurrence. Although the number of cases was small, this study suggests that axillary recurrence following a negative sampling procedure is not commonly due to missed axillary node metastases.     

PET/CT诊断乳腺癌及腋窝淋巴结状态的作用评价

目的：评价PET／CT诊断乳腺癌和腋窝淋巴结转移的临床价值。方法：对33例疑似乳腺癌病人进行PET／CT检查，定性分析肿瘤病灶、淋巴结摄取氟脱氧葡萄糖（FDG）的程度，半定量测量标准摄取值（SUV），根据乳腺和淋巴结的FDG摄取强度诊断乳腺癌和淋巴结转移，检验SUV与乳腺癌分化程度、有丝分裂计数的关联性。结果：PET／CT诊断乳腺癌和腋窝淋巴结转移的敏感度、特异度和精确度分别为92．6％、100％、93．9％和82．3％、90％、85．2％；SUV与乳腺癌分化程度、有丝分裂计数显著相关（P〈0．05）；诊断乳腺癌的Kappa指数=0．835，μ=8．48，（P〈0．01）。结论：PET／CT诊断乳腺癌和腋窝淋巴结转移的敏感度、特异度较高，作为一种非侵袭性检查方法，可提供乳腺癌在活体内的多方面生物学信息，为选择合理的手术方式及新辅助化疗提供参考，弥补传统检查方法的不足。     

Multicentre study of ultrasonographically guided axillary node biopsy in patients with breast cancer

BACKGROUND: Axillary lymph node dissection is still performed as a staging procedure since lymph node status is the most important prognostic factor in patients with breast cancer. Sentinel node biopsy may replace routine axillary lymphadenectomy, especially in patients with small breast cancers. This study investigated whether ultrasonographically guided fine-needle aspiration cytology (FNAC) of the axillary lymph nodes in clinically node-negative patients was an accurate staging procedure to select patients for sentinel node biopsy. METHODS: One hundred and eighty-five consecutive patients were included. All had axillary ultrasonography and detected nodes were categorized according to their dimensions and echo patterns. Ultrasonographically guided FNAC was carried out if technically possible. These results were compared with the results of the sentinel node biopsy and subsequent axillary dissection. RESULTS: In 116 patients no lymph nodes were detected by ultrasonographic imaging. Of 69 patients with visible nodes, 31 had malignant cells on FNAC. There were no false-positive results. Some 87 of 185 patients had axillary metastases on definitive histological examination. Ultrasonography was sensitive in patients with extensive nodal involvement. Failure of the examination was caused by problems learning the method, difficulty in puncturing small lymph nodes and sampling error. CONCLUSION: In patients without palpable axillary nodes, a sentinel node biopsy could be avoided in 17 per cent since ultrasonography combined with FNAC had already diagnosed axillary metastases. The method is particularly valuable in larger breast cancers.