Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients

The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases. © 1993 Wiley-Liss, Inc.     

C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.     

The role of internal mammary lymph node metastases in the management of breast cancer

We reviewed the literature regarding internal mammary lymph node metastasis in the management of breast cancer. Internal mammary dissection or radiotherapy provides no survival advantage in breast cancer patients. However, internal mammary nodal metastasis is an important independent prognostic factor. Patients with such metastases are candidates for systemic adjuvant hormonal therapy and/or chemotherapy. Moreover, in patients with histologically confirmed internal mammary metastases, irradiation of the nodes is appropriate for local control. Noninvasive techniques, such as internal mammary lymphoscintigraphy, parasternal sonography, computed tomography, and magnetic resonance imaging, are not satisfactory for the practical diagnosis of internal mammary metastasis. At present, biopsy of the internal mammary nodes in the first and second intercostal spaces is indicated for assessing nodal status and planning treatment.     

Aldehyde dehydrogenase 1-positive cells in axillary lymph node metastases after chemotherapy as a prognostic factor in patients with lymph node-positive breast cancer

BACKGROUND:

Aldehyde dehydrogenase 1 (ALDH1)‐positive cells exhibit stem‐like or progenitor ability and have been considered a clinically important diagnostic and therapeutic target in patients with breast cancer. In this study, the authors evaluated responsiveness to chemotherapy of ALDH1‐positive cells in primary and metastatic lesions and its relation to prognosis for patients with lymph node‐positive breast cancer.

METHODS:

In total, 115 patients who had breast cancer with cytologically confirmed lymph node metastases and who underwent surgery after neoadjuvant chemotherapy (NAC) were evaluated. By using ALDH1 immunohistochemistry in core‐needle biopsy specimens of the primary tumor, cytology samples of axillary lymph nodes before NAC, and pathologic samples of each after NAC, the clinical significance of ALDH1‐positive cell status was evaluated in primary and metastatic lesions before and after NAC.

RESULTS:

The presence of ALDH1‐positive cancer cells, but not ALDH1‐negative cancer cells, in primary and metastatic lesions after NAC was associated with a worse prognosis. In multivariate analysis, only ALDH1‐positive cells in metastatic lesions after NAC correlated with overall survival. The responsiveness of ALDH1‐positive cells to chemotherapy differed between primary and metastatic lesions, and the findings indicated that ALDH1‐positive cells in metastatic lesions after NAC may clinically precede those in the primary lesion.

CONCLUSIONS:

The responsiveness of ALDH1‐positive cells to chemotherapy in primary and metastatic lesions and its prognostic significance were clarified in patients with breast cancer. The authors concluded that ALDH1‐positive status may represent a surrogate marker as a new concept in patients with lymph node‐positive breast cancer. Cancer 2012. © 2011 American Cancer Society.     

Sentinel node biopsy in the evaluation of the internal mammary node chain in patients with breast cancer

AIMS AND BACKGROUND: In patients with breast cancer the presence of internal mammary chain (IMC) metastases changes tumor staging, and the occurrence of IMC drainage is quite common in breast cancer. Nevertheless, IMC dissection is not a routine procedure in modern surgical approaches towards breast cancer. We therefore need minimally invasive techniques for accurate assessment of the IMC nodal basin. The aim of this study was to investigate whether sentinel node biopsy (SLNB) could offer a solution. METHODS AND STUDY DESIGN: From November 1997 to June 2001 143 female patients who were eligible for breast cancer surgery were included in the study. All patients had T1 breast cancer and clinically negative axillae. Patients were submitted to preoperative lymphoscintigraphy with subsequent SLNB. We used a 99m-technitium nanocolloid tracer (Nanocoll) that was injected peritumorally so as to have about 10 MBq of radioactivity at the time of surgery. Scintigraphy was performed about 17 hours after tracer administration. During surgery, lymphoscintigraphic imaging and a gamma ray detection probe were used to locate the sentinel node. Histological examination after embedding in paraffin was usually requested and multilevel sectioning of the sentinel node (SLN) was performed, with hematoxylin and eosin staining and immunohistochemistry. RESULTS: Preoperative lymphoscintigraphy localized SLNs in the IMC basin in 27 of 143 patients (18.9%). Harvesting of IMC-SLNs based on lymphoscintigraphy results was successful in 20 of 27 patients (74.1%). Histological examination revealed micrometastases in four of the 20 harvested nodes. One of these patients showed no axillary drainage and no axillary lymph node dissection was therefore performed. In the remaining three patients also axillary SLNs were harvested, which turned out to be free from metastatic involvement. CONCLUSIONS: In our experience lymphoscintigraphy with SLNB was an accurate method to detect IMC metastases in patients with breast cancer. We recommend peritumoral tracer injection and a reasonable interval between injection and scintigraphy. IMC-SLN biopsy did not result in any serious additional complications or morbidity. In our study this approach led to improved cancer staging: four of 20 harvested IMC-SLNs proved to be micrometastatic. None of these four patients had metastatic axillary SLNs. Exclusive drainage to the IMC is present in only a small number of breast cancer patients, and our results suggest that it is possible to avoid unnecessary axillary node dissection in such cases.     

Isolated internal mammary sentinel lymph node metastasis in two breast cancer patients

 Lymphatic mapping with sentinel node biopsy may lead to more accurate staging of breast cancer patients. Two patients with sentinel nodes in the internal mammary node chain are described. These nodes were visualized on lymphoscintigraphy images and harvested by the surgeon. They were shown to contain tumor cells in the absence of axillary involvement. This led to upstaging and to a change in the subsequent management. Received: May 16, 2002 / Accepted: July 1, 2002 Correspondence to:S.J. Haryono     

The lymph node ratio as prognostic factor in node-positive breast cancer

BACKGROUND AND PURPOSE: The clinical records of the node-positive breast cancer patients treated at our department were reviewed, to evaluate if there is a correlation between the ratio of involved axillary lymph nodes and the overall and cause specific survival. PATIENTS AND METHODS: From 1984 until July 2001, 2073 files from patients with an invasive breast carcinoma were submitted to retrospective analyses. In 810 cases, a node positive status was diagnosed. All pT-stages were included. The total number of dissected nodes (pNtot) and the number of involved nodes (pN+) were available for 741 patients. The ratio of nodal involvement (pN+%) was categorized into three groups, pN+%< or =10% (n = 212) between 11 and 50% (n = 346) and between 51 and 100% (n = 183). RESULTS: The actuarial overall survival (OS) at 5 and 10 years was, respectively, 78.2 and 59.1%. Cause specific survival (CSS) rates were, respectively, 83.6 and 69.1%. In univariate analyses, age (P = 0.01), grade (P = 0.02), pT-stage (P < 0.0001), chemotherapy (P = 0.0002), the number of involved nodes < or =3 versus >3 (pN+) (P < 0.0001) and ratio pN+% (P < 0.0001) were associated significantly with overall survival. A multivariate analysis using the Cox proportional hazards model found that pN+% was the most significant prognostic factor; pN+lost significance when pN+% was taken into account. CONCLUSIONS: The percentage of positive lymph nodes in an axillary lymph node dissection appears to be an important prognostic factor for survival. The nodes ratio improved on the absolute numbers of involved axillary lymph nodes for assessment of prognosis.     

Parity as a prognostic factor in young breast cancer patients

Data were analyzed concerning 219 female breast cancer patients less than 36 years of age who were diagnosed and treated in the Province of Saskatchewan, Canada, during 1946-72. Pathology slides were available for review on 171 of these patients, and invasive breast cancer could be confirmed in 136. Nulliparous patients had more favorable age-adjusted survival rates than parous patients for the total patient group and for those patients whose tumor was verified to be invasive cancer on pathologic review. Adjustment for potential confounding factors indicated that differences in survival among parity groups could be explained to a substantial degree by differences in distribution over node status and the nuclear grade of the primary tumor. Because these factors relate to the biologic behavior of breast cancer and because the distributions of these factors were significantly associated with the parity categories utilized in the analysis, the data provide some evidence that parity influences the behavior of breast cancer in young women.     

Legumain expression as a prognostic factor in breast cancer patients

Invasive tumor cells and their microenvironments are enriched with a broad spectrum of different proteases. Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of solid tumors. However, there is no data available identifying the relationship of legumain expression and clinicopathologic or biological variables in invasive breast cancer. For the first time, the prevalence of legumain expression in invasive breast cancer (n = 432) and non-neoplastic breast tissues (n = 128) was investigated by immunohistochemistry. Three staining patterns were observed in the cytoplasm: diffuse positivity, tiny dots and vesicles. Whereas vesicular positivity in the majority of tumor cells was significantly correlated to an adverse outcome, cytoplasmic and dot-like staining showed no prognostic effect. Vesicular positivity was observed in 24% of carcinomas, but only in one case of non-neoplastic breast tissue (<1%; proliferative mastopathy). This staining pattern was found to be independent of other factors analysed as grading, nodal status or HER2 expression. Besides being of prognostic value, legumain might prove to be an important predictive factor in breast cancer, since its unique cleavage specificity is already used in prodrug activation strategies. Jessica Gawenda and Frank Traub contributed equally to this study.     

Quantitative ultrasound as a predictor of node metastases and prognosis in patients with breast cancer

BACKGROUND: A retrospective study was performed to determine whether preoperative quantitative ultrasound assessment could predict axillary lymph node metastases and prognosis in patients with breast cancer. We focused on the presence of a halo, which is one of the features of breast cancer on ultrasound and represents reflections from the invading margin around infiltrating malignancies. METHODS: We evaluated ultrasonography from 187 infiltrating breast carcinoma patients with tumors 5 cm or less in greatest dimension (T1, T2). Using computer image analysis, the halo area (H) and the sum of the area of halo and internal echo (total tumor area (T)) were measured, and the ratio of halo to entire tumor (H/T, halo ratio) was calculated and compared with lymph node status and prognosis. RESULTS: The mean of the halo ratio was 0.38+/-0.13. Using the value of 0.42 as a cut-off, the high halo ratio group had significantly worse prognoses for both overall and disease-free survival at 49 months in median follow-up (p <0.001 and p <0.0005, respectively). The specificity of a high halo ratio in the T1 classification for predicting axillary node metastasis was 83.1%, with a negative predictive value of 86.8%. In patients with tumors 1.0 cm or smaller, the negative predictive value was 100%. In a multivariate analysis, halo ratio was an independent predictor of disease-free survival of breast carcinoma patients (p =0.0232). CONCLUSIONS: Preoperative quantitative ultrasound may be a useful non-invasive method for predicting the presence of axillary lymph node metastases and prognosis in patients with primary breast cancer.     

乳腺癌内乳区淋巴结转移研究进展

 内乳区淋巴结的转移状况是乳腺癌的独立预后指标,也是乳腺癌分期的重要依据之一。内乳区淋巴结转移的患者预后较差。内乳区淋巴结的总体转移率为18 %～33 %,仅有内乳区淋巴结转移而无腋窝淋巴结转移的发生率为2 %～11 %,其转移受腋窝淋巴结状况、患者年龄、原发肿瘤的位置和特点等多因素影响。随着前哨淋巴结活检技术的不断发展,内乳区前哨淋巴结活检术可能以最小的风险评估内乳区淋巴结状况,并进一步完善乳腺癌的淋巴结分期,有助于为患者制定更为准确的个体化治疗方案。     

Efficacy of extrapleural internal mammary node dissection in breast cancer

The results of extended radical mastectomy for breast cancer in 180 randomized patients treated at this department between 1965 and 1984 are reported. About 18% of the women with breast cancer had internal mammary lymph node metastasis. The incidence of metastasis in internal mammary lymph nodes increased from 9.5% when the tumor was locate in the outer half to 24.7% when it was in the center or inner half. The increase in the number of axillary lymph node metastasis was correlated with the increase in the incidence of internal mammary lymph node metastasis. The five-year survival rate of patients with no internal mammary lymph node involvement was better than that of involvement (81% versus 47%). But when the internal mammary nodes alone were involved without axillary lymph node metastasis, 83% of the patients survived for five years.     

Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan

PURPOSE: To analyze the frequency in determining pathologically proven metastatic involvement of internal mammary nodes (IMN) after sentinel lymph node (SLN) technique in breast cancer and to evaluate the implications for radiotherapy (RT) management of patients. METHODS AND MATERIALS: Two hundred and twenty-five patients who underwent lymphatic mapping for early breast cancer treated with breast-conserving surgery and radiation (80%) or mastectomy (20%) were evaluated. There were two phases in the study: the validation phase (105 patients, 52 T1, 53 T2 < or = 4 cm), and the application phase (120 patients, 70 T1, 50 T2 < or = 2.5 cm). In the validation, if a drainage pathway to the IMN was identified, no biopsy was performed in this phase. In the application, if the study showed metastases in the IMNs, biopsy was performed. When histologically proven IMN metastases were detected, RT was included on the IMN chain planned with a 3D treatment system using conformal techniques. At the beginning of the study the injection site was subdermal and subsequently, the injection site was changed to peritumoral and intratumoral to search for IMN. RESULTS: In 31 patients of 225 (14%) hot spots were observed in the internal mammary chain (11.5% and 17.2% in the validation and application phases, respectively). In the validation phase, in 11 cases (11.5%) IMN drainage was observed, and in the application phase, in 20 cases (17.2%). Sampling of the internal mammary basin based on lymphoscintigraphy results was successful in 69% of the cases (14 of 20) and revealed metastatic involvement in 14% (2 of 14). This represents incidence of only 1.7% (2 of 116) in early breast cancer patients with SLN study in the application phase. In both cases the axillary SLN was also positive. Both patients with metastatic involvement of the IMN area received RT on the IMN chain next to the remaining breast after conservative surgery. CONCLUSIONS: We can conclude that 14% of the patients with intraoperative drainage into the IMN surgical examination of the lymph nodes had pathologically positive metastases. The percentage in pathologically proven metastatic involvement of IMN after the SLN technique in early breast cancer is low, but it is not negligible. Moreover, it is expected to increase since the international recommendations have established a 3-cm cutoff for practicing the SLN technique. Although the real value of IMN irradiation in early breast cancer is not known, including this chain in postoperative radiotherapy is not recommended unless pathologically proven IMNs have been produced by the SLN technique. To avoid overdosage or underdosage in the joint between the medial tangential and IMN fields, an individualized 3D dosimetry study is mandatory to enhance dose distribution and reduce the heart volume to lessen side effects.     

Efficacy of internal mammary node dissection in the treatment of breast cancer.

The present study compares clinical and pathological findings and survival data from 410 patients who have undergone extended radical mastectomies in our hospital during the 20 years from 1967 with those derived from 261 who underwent mastectomies without dissections of the internal mammary nodes, in order to determine the value of additional internal mammary node dissection following standard radical mastectomy. Extended radical mastectomy was used in 289 of 361 (80.1%) patients with medial tumors, and in 121 of 310 (39.0%) with lateral tumors. Metastases to the internal mammary nodes were found in 18.5% (76) of all patients, in 20.4% (59) of the patients with medial tumors and in 14.0% (17) of those with lateral tumors. Of the patients with medial tumors, internal mammary node metastases were found in seven of 44 (15.9%) at TNM Stage I, and the rate of metastases rose with advances in stage. Internal mammary node metastases alone, without those to the axillary nodes, were found in 14 patients (4.8%) with medial tumors and in two with lateral tumors. The 10-year survival rate in patients with medial tumors and metastases to the internal mammary nodes only was 67.0%, which was as good as that in patients with metastases to the axillary nodes only. In conclusion, extended radical mastectomy was valuable in the treatment of relatively early medial breast cancer at TNM Stages I and II.     

Aneuploidy as a prognostic factor in breast cancer

The predictive value of nuclear DNA content in mammary carcinoma is still under debate in spite of several reports indicating a relationship between DNA ploidy and prognosis. The impact of differences in methodology on the evaluation of DNA data is discussed, and a recent study demonstrating DNA ploidy as a statistically significant prognostic variable on a prospective material of breast cancer patients is presented.     

Age as a prognostic factor in breast cancer

The influence of age on survival was studied in an unselected series of 31,594 females with breast cancer reported to The Cancer Registry of Norway during 1955-1980. The prognosis was best in patients aged 35 to 49 years, and poorest in the older (greater than or equal to 75 years) and the younger patients (less than or equal to 34 years). These trends were present in all stages and periods of diagnosis. The poor outcome among the older patients may, in part, be related to less aggressive treatment, while differences in treatment procedures hardly explain the poor prognosis among the younger patients.     

Age as a prognostic factor in breast cancer

Long-term survival was evaluated in a total of 12,319 women with first breast cancer, comprising 94.9% of virtually all women with first breast cancers diagnosed in Sweden in 1959 through 1963. After correction for the expected mortality, it was found that age at diagnosis was an important predictor of the probability of escaping the risk of dying of breast cancer (relative survival), with a regular trend toward a more favorable course in younger women. This difference between the age groups is apparent as early as 5 years after diagnosis and increases throughout the period of observation. Thus the relative 20-year survival rates +/- 95% confidence limits were 51.3 +/- 3.8%, 41.2 +/- 3.4%, 34.2 +/- 3.8%, and 16.6 +/- 6.3% at ages 40 through 44, 50 through 54, 60 through 69, and 70 through 79 years, respectively. Patients younger than 40 years diverged from the general trend, with a survival rate of 44.1 +/- 4.6% at 20 years.     

Aneuploidy as a prognostic factor in breast cancer

The predictive value of nuclear DNA content in mammary carcinoma is still under debate in spite of several reports indicating a relationship between DNA ploidy and prognosis. The impact of differences in methodology on the evaluation of DNA data is discussed, and a recent study demonstrating DNA ploidy as a statistically significant prognostic variable on a prospective material of breast cancer patients is presented.     

The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases.

AIMS: The aim of the study was to estimate the prevalence of and risk factors for non-sentinel node (NSN) involvement in breast cancer patients with sentinel node (SN) micrometastases. METHODS: Eighty-four patients with SN micrometastases were included. Both the SN and NSN were examined using serial sectioning and immunohistohemistry. Various indices were evaluated as possible risk factors for NSN involvement. RESULTS: NSN involvement was found in 22/84 patients. The median size of the NSN metastases was 1.25 mm (0.01-12 mm). The NSN metastases were larger than 2 mm in 8 patients and smaller than 0.2 mm in 6 patients. NSN involvement was observed in 14/35 patients with metastatic findings in all removed SN. Three of the 23 patients with 2 or 3 tumour negative SN had NSN metastases. None of the 12 patients with 4 or more uninvolved SN had NSN metastases. NSN involvement could not excluded by other patient, tumour or sentinel node related factors. CONCLUSIONS: Every fourth patient will have residual disease in the axilla, 10% even large metastases, if axillary clearance is omitted in patients with SN micrometastases. The risk of NSN involvement seems negligible in patients with a single SN micrometastasis and four or more healthy SN harvested.     

Metastatic lymph node ratio as a prognostic factor in gastric cancer.

BACKGROUND: There is an association between the number of resected lymph node and the number of metastatic lymph nodes in gastric cancer, suggesting that pN category could be influenced by the extension of the lymphadenectomy. This study evaluates this association and proposes a comprehensive use of the ratio as prognostic factor. METHOD: Review of 183 consecutive patients with gastric adenocarcinoma. The association between the number of resected lymph nodes and the number of metastatic lymph nodes was analysed and evaluated with other prognostic factors. RESULTS: The number of lymph node metastases increased with the number of resected lymph nodes. The lymph node ratio was a better prognostic factor than the number of metastatic lymph nodes. CONCLUSIONS: The metastatic lymph node ratio seems to be a good prognostic factor, but needs further evaluation.