Internal Mammary Metastases Research Articles

Abstract P6-03-09: Internal mammary lymph node biopsy during free flap breast reconstruction: Accurate oncologic staging leads to change in adjuvant therapies

Abstract Introduction: Accurate breast cancer staging, including nodal status, is essential for optimal management of adjuvant therapies leading to improved disease-specific and overall survival. Lymphatic drainage of the breast is known to involve both axillary and internal mammary (IM) lymph node basins. While IM nodal metastases represent advanced cancer stage, sampling is not routinely advocated due to relative lack of accessibility and the assumption that IM node positivity rarely alters adjuvant therapies. The current study analyzes the incidence of IM nodal metastases sampled during routine IM vessel exposure for free flap breast reconstruction and changes in adjuvant treatment. Methods: A retrospective analysis of patients with positive IM lymph node biopsies at the time of free flap breast reconstruction following mastectomy between September 2008 and December 2015 was performed. Patients undergoing reconstruction following prophylactic mastectomy and reconstruction where IM vessels were not exposed were excluded. Prevalence of neoadjuvant therapies and previous lumpectomy with axillary lymph node (LN) sampling were recorded. Tumor size, location, and axillary LN status were obtained from final pathologic analysis. Prognostic factors and proliferative index (Ki-67) for the primary breast lesion were utilized to determine oncologic subtype. Change in adjuvant therapies (chemotherapy or external beam radiation) based solely on IM LN positivity was calculated. Results: During the study period, 2057 patients fit study criteria. Twenty eight (1.3%) patients were found to have IM LN metastases and comprised the study population. Mean age of patients with positive IM metastases was 49 years with pre-reconstruction chemotherapy or radiation administered in 50% or 54% of cases, respectively. Five (18%) patients had previously undergone lumpectomy with axillary sampling prior to mastectomy and reconstruction for cancer recurrence. Mean tumor size was 3.1 cm (range 0.4 to 10 cm) with tumor location evenly distributed among all four quadrants. Although statistical significance between subtypes was not identified, luminal B (42.9 percent) was the most common subtype present. Ten (36%) patients had isolated IM lymph node metastases with negative axillary nodal disease. Patients with both axillary and internal mammary disease had larger lesions (4.4 cm vs. 2.5 cm), increased prevalence of pre-reconstruction chemotherapy (65 percent vs. 20 percent) and radiation (71 percent vs. 20 percent). Multivariate analysis did not identify any significant independent factors associated with isolated IM lymph node metastases. Ultimately, 17 (63%) patients had a change in their adjuvant therapy (additional chemotherapy or IM radiation therapy) based on positive IM LN disease. Conclusion: Despite the low overall incidence of IM LN metastases, IM LN biopsy at the time of free flap breast reconstruction is recommended. In 36% of cases, nodal metastases were isolated to the IM nodes. Interestingly, a significant percentage (18%) of patients had previously undergone lumpectomy and axillary sampling. Identification of IM metastases significantly influenced adjuvant therapies in a majority of cases. Citation Format: Ochoa O, Pisano S, Chrysopoulo M, Ledoux P, Arishita G, Nastala C. Internal mammary lymph node biopsy during free flap breast reconstruction: Accurate oncologic staging leads to change in adjuvant therapies [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-09.

Results of tailored treatment for breast cancer patients with internal mammary lymph node metastases

Although the internal mammary (IM) lymph node status is a major prognostic factor in breast cancer, IM nodal staging is not common practice. In order to improve nodal staging, we have routinely performed IM sentinel node (SN) biopsy and have adjusted adjuvant treatment accordingly. We reviewed the outcome of these patients. Data from 764 patients were available for follow-up. A total of 406 patients had no lymph node metastases (group 1), 330 patients had axillary metastases (group 2), 7 patients had IM metastases only (group 3) and 21 patients had both axillary and IM metastases (group 4). Mean follow-up was 46 months. Prognosis did not appear to be worse for patients with IM metastases compared to those with axillary metastases only, which might indicate that they benefit from improved staging and tailored adjuvant treatment algorithms. However, long-term follow-up data, preferably in larger series, are needed to support our findings.

The role of FDG-PET for preoperative evaluation of regional lymph node metastases in locally advanced breast cancer.

Abstract Abstract #4021 Backgound: The aim of this study was to evaluate the role of FDG-PET in detecting regional lymph node metastases in locally advanced breast cancer.
 Methods: FDG-PET was performed in 114 women with locally advanced breast cancer. Among them, 7 were with primary tumor larger than 5cm, 18 were with inflammatory breast cancer, and 89 were with clinically palpable axillary lymph node metastases. FDG uptakes of axillary, internal mammary, and supraclavicular lymph node were correlated by comparing pathologic and radiographic findings.
 Results: The sensitivity, specificity, and positive predictive value of FDG-PET for detection of axillary lymph node metastases in 83 patients who did not receive neoadjuvant chemotherapy were 91%, 33.3 % and 94.7% respectively. Among the 83 patients, 4 were with false-negative and 6 were with false-positive. Those for detection of axillary lymph node metastases in 12 patients who received neoadjuvant chemotherapy were 55.6%, 100%, and 100% respectively, and 4 of them were with false-negative and no one was with false-positive results. The sensitivity and positive predictive value of combined assessment of clinical examination and ultrasound scan on axillary node metastases were 92.1% and 93.3% in 81 patients. Those of combined assessment of clinical examination, ultrasound scan, and PET were 100% and 95.7% in 69 patients. FDG uptake in internal mammary node was seen in 14 out of 114 patients (12.2%). The positive predictive value of FDG-PET for detection of internal mammary metastases in 9 patients with pathologic confirmation was 75%. 6 of them were with true-positive, 2 were with false-positive, and 1 was false-negative. Among the 6 true positive patients, 3 were not detected internal mammary metastases in ultrasound scan. FDG uptake in the supraclavicular node was seen in 22 out of 114 patients (19.2%). The positive predictive value of FDG-PET for detection of supraclavicular metastases in 12 patients with pathologic confirmation was 58.3%. 7 of them were with true –positive and 5 were with false-positive. 1 of 7 true-positive patients was not detected supraclavicular lymph node metastases in ultrasound scan.
 Conclusions: The sensitivity of FDG-PET for detection of axillary lymph node metastases was higher than that of FDG-PET for detection of internal mammary or supraclavicular lymph node. The addition of FDG-PET to standard work-up of locally advanced breast cancer patients could provide a more precise evaluation of regional lymph node metastases. Positive combined assessment of clinical examination, ultrasound scan and PET on axillary node metastases also could be an indication for full ALND without SNB. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4021.

Clinical relevance of internal mammary node drainage in sentinel node biopsy for breast cancer

519 Background: This study was designed to identify the frequency of internal mammary(IM) drainage in patients undergoing sentinel node biopsy(SNB) in a controlled clinical trial. The clinical relevance of internal mammary SNB as a method to improve nodal staging and treatment in breast cancer is investigated. Methods: A total of 1,139 patients with invasive breast cancer underwent SNB based on a standardised protocol using Tc 99m albumin colloid and Patent Blue V injected peritumorally. In 707 patients who participated in the validation phase, SNB was followed by standard axillary treatment in the same operation. Results: Lymphoscintigraphy showed IM sentinel nodes in 106 patients(9%), and IM drainage was identified perioperatively in an additional 14 patients(1%) using the gamma probe. Sampling of the IM basin, was done in 60 of the 120 patients (50%) with IM drainage. Three patients had a pneumothorax and 3 experienced bleeding during IM sampling. IM metastases were detected in 8 of the 60 patients(13%...

Internal Mammary Node Drainage and its Role in Sentinel Lymph Node Biopsy: The Initial ALMANAC Experience

This study was designed to identify the frequency of internal mammary drainage in patients undergoing sentinel lymph node (SLN) lymphoscintigraphy in a controlled clinical trial. The practicability and relevance of internal mammary SLN biopsy as a method to improve nodal staging and treatment in breast cancer were investigated. A total of 707 evaluable patients with invasive breast cancer underwent SLN biopsy based on lymphoscintigraphy, intraoperative γ probe detection, and blue dye mapping using technetium Tc 99m albumin colloid and Patent Blue V injected peritumorally. This was followed by standard axillary treatment in the same operation in all patients. Lymphoscintigraphy showed internal mammary sentinel nodes in 62 patients (9%), and internal mammary drainage was identified perioperatively in an additional 7 patients (1%) using γ probe detection. Sampling of the internal mammary basin, based on the results of lymphoscintigraphy and γ probe detection, was done in 31 of 69 patients (45%). One patient had a pneumothorax and 2 experienced bleeding during internal mammary sampling. Internal mammary metastases were detected in 4 of 31 patients (13%). In 2 of the patients (6%), internal mammary nodes (IMNs) showed metastatic involvement without accompanying axillary metastases. One of these 2 patients would have received adjuvant endocrine systemic therapy because of the characteristics of the tumor, but may not have been recommended to receive adjuvant chemotherapy. Sampling of the internal mammary basin led to a change of management in these 2 patients, ie, institution of adjuvant chemotherapy. Therefore, a change in management occurred in only 2 of the 69 patients in our series, but 38 patients with unbiopsied "hot" IMNs remained with unknown internal mammary status. Biopsy of IMNs alters staging in few patients, and the impact on indication for adjuvant treatment was low. Internal mammary SLN biopsy may be associated with some additional morbidity. Current evidence suggests that internal mammary SLN biopsy is still a research tool.

Lymphoscintigraphic visualization of internal mammary nodes with subtumoral injection of radiocolloid in patients with breast cancer.

To determine whether subtumoral injection of radiocolloid is useful for lymphoscintigraphic visualization of the internal mammary node and in sentinel lymph node (SLN) biopsy of the axilla in breast cancer patients. The presence of retromammary lymphatics connecting to the axillary and internal mammary basins has been demonstrated by early anatomic studies. Thus, it is hypothesized that some lymph, especially that from the parenchyma under the tumor, may drain into both the axillary and internal mammary basins. Patients (n = 196) with T1-2, N0 breast cancer underwent preoperative lymphoscintigraphy with radiocolloid (technetium 99m tin colloid) injection into various sites of the breast, followed by SLN biopsy using the combined method with blue dye. Patients were divided into four groups: group A (n = 41), peritumoral injection of both radiocolloid and blue dye; group B (n = 70), periareolar radiocolloid and peritumoral blue dye; group C (n = 45), intradermal radiocolloid and periareolar blue dye; and group D (n = 40), subtumoral radiocolloid and intradermal blue dye. A retrospective analysis of 1,297 breast cancer patients who underwent extended radical mastectomy with internal mammary node dissection was also conducted to determine the relationship between vertical tumor location (superficial or deep) and frequency of axillary and internal mammary node metastases. One patient (2%) in group A, 3 (4%) in group B, 0 (0%) in group C, and 15 (38%) in group D exhibited hot spots in the internal mammary region on lymphoscintigraphy (P <.001, group D vs. the other groups). The concordance rate of radiocolloid and blue dye methods in detection of SLNs in the axillary basin was significantly lower in group D than in the other groups. In contrast, the mismatch rate (some SLNs were identified by radiocolloid and other SLNs were identified by blue dye, but no SLN was identified by both in the same patient) was significantly higher in group D than in the other groups. In patients treated with extended radical mastectomy, positivity of axillary and internal mammary metastases was significantly higher in patients (n = 215) with deep tumors than those (n = 368) with superficial tumors. These results suggest the presence of a retromammary lymphatic pathway from the deep portion of the breast to both axillary and internal mammary basins, which is distinct from the superficial pathway. Therefore, SLN biopsy with a combination of subtumoral and other (peritumoral, dermal, or areolar) injections of radiocolloid will improve both axillary and internal mammary nodal staging.

Clinical relevance of internal mammary node mapping as a guide to radiation therapy

Background: The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy. Methods: From April 1998 to November 2000, 1,470 patients underwent lymphatic mapping for breast cancer and were prospectively entered into the breast database. The combined technique method was used, consisting of both isosulfan blue dye and technetium-99 labeled sulfur colloid. Patients with inner quadrant lesions and suspicion for internal mammary metastasis had preoperative lymphoscintigraphy. Those with internal mammary radioactivity noted by either lymphoscintigraphy or gamma probe underwent removal of the internal mammary sentinel nodes. Results: Thirty-six of the 1,470 (2.4%) patients mapped had at least 1 internal mammary lymph node removed. Inner quadrant lesions were present in 24 of the 36 (67%) IMN mapped patients. Of the 36 patients mapping to the IM area, 5 (14%) had at least 1 IM node positive. Two of the 5 (40%) had only IM metastasis, with 1 of these patients having 5 of 5 IMN positive and no disease detected in her axilla. A total of 2 of the 5 (40%) IM positive patients had more than 1 IMN positive. Twenty-eight of the 36 (78%) IM node harvested patients had preoperative lymphoscintigraphy, with 18 (64%) IMN appearing on imaging. Complications occurred in 3 of the 36 (8%) IMN mapped patients, without clinical significance. Conclusions: Mapping to the IMN basin with the finding of metastasis results in N3 disease by the current staging system. The consequence for these patients is radiation therapy to the IMN basin. It is significant to note that 14% (5 of 36) were upstaged as result of IMN detection and 40% (2 of 5) had multiple positive IMNs. Substantial disease was detected in these 5 patients necessitating additional radiation therapy while avoiding IM radiation and its attendant complications in 86% of patients mapping to the IM basin.

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.

Clinical and biological prediction of axillary and internal mammary lymph node metastases in breast cancer

We assessed the relationships among histological axillary (AX) or internal mammary (IM) metastases and clinical and biological variables, and then attempted to evaluate their predictive values for AX and IM metastases in 128 patients with invasive breast cancer. As the results, these clinical and biological variables were significantly correlated with AX and IM metastases. However, a metastatic index calculated from clinical and biological variables was not much better in prediction of the AX metastases than axillary nodal status, whereas it was useful to predict the IM metastases. Thus, the predictive ability was still limited. Since accurate prediction of AX and IM metastases is critical to therapeutic choice, however, further study would be required.

Risk of internal mammary lymph node metastases and its relevance on prognosis of breast cancer patients.

The risk of internal mammary chain metastases according to some parameters and its prognostic relevance was evaluated on the basis of the experience collected at the National Cancer Institute of Milan where, from January 1965 to December 1980, 1085 patients were submitted to Halsted mastectomy plus internal mammary chain dissection. A multivariate analysis was carried out, resorting to a multiple linear regression with logistic transformation of the dependent variable. The selection of prognostic factors has been performed with a step-down approach. The frequency of metastases to internal mammary chain nodes was evaluated according to four criteria: age, site and size of primary tumor, and presence of axillary metastases. Data of this series indicate that the frequency of internal mammary node metastases is significantly associated with the age of the patients (younger patients have a higher risk) (p = 0.006) with the size of primary tumor (p = 0.006) with the presence of axillary node metastases (p = 10(-9). Patients with both axillary and internal mammary positive nodes have a very poor prognosis (10-year survival 37.3%) while patients with either axillary metastases only or internal mammary metastases only have an intermediate less grave prognosis (59.6% and 62.4%, respectively). As regards the risk of internal mammary nodes involvement, it appears that knowing the age, the size, and the axillary nodes status, it is possible to calculate with good approximation the probability of their invasion.

乳癌の進展とリンパ節転移に関する研究

Internal mammary lymph node metastasis, sinus histiocytosis and follicular hyperplasia of 150 cases of breast cancer patients were studied. Axillary metastasis was 48% and internal mammary metastasis was 30%. Patients having one lymph node metastasis of axillary nodes were 33.3% metastasis in internal mammary node. Seven cases (10.9%) in 64 cases of Stage I patients had internal mammary metastasis. Therefore, the internal mammary node dissection will be necessary. Low grade of sinus histiocytosis and follicular hyperplasia group have high average of internal mammary metastasis and metastatized lymph node numbers were also considerably.

Enlarged mastectomy for breast cancer. Review of 1,213 cases.

It may be concluded from the whole case material that:1. About 22 per cent of the women with operable breast cancer had internal mammary metastases.2. Even tumors of the lateral quadrants rarely metastasize to the internal mammary lymph nodes.3. Survival among cases with internal mammary metastases only is very high (70-80 per cent at 5 years).4. In our experience postoperative radiotherapy did not improve the 5 year survival.

SURGICAL TECHNIC OF EXCISION OF ISOLATED INTERNAL MAMMARY METASTASES IN PATIENTS WHO HAVE UNDERGONE RADICAL MASTECTOMY

Six patients with a solitary internal mammary metastasis observed 1 to 15 years after a previous radical mastectomy, were surgically treated. The surgical procedure required a wide toracectomy, with removal of the edge of the sternum and of a portion of the second, third and fourth rib; the skin over the tumor and the underling pleura were removed in bloc with the specimen. The repair of the chest-wall defect was obtained with a full-thickness-flap-pedicle graft developed either from skin and subcutaneous tissues of chest and abdominal walls or from the opposite breast.

An Aspect of Internal Mammary Metastases From Carcinoma of the Breast

An Aspect of Internal Mammary Metastases From Carcinoma of the Breast

Excision of the internal mammary lymph nodes in the treatment of breast cancer

From 1948 to May 1961, 304 patients underwent radical mastectomy with dissection of the internal mammary lymph node chain at the Cancer Institute of Milan. Out of these, 199 were submitted to extrapleural removal of internal mammary lymph nodes, and 105 to an «en bloc » removal, with sterno-costal toracectomy. Of the 305 cases operated upon by the two different techniques, 72 (23.7 %) had internal mammary metastases. The internal mammary involvement was found to be frequent also in tumours of the lateral quadrants (20%). In addition, it could be demonstrated that a relation exists between size of the mammary tumour and frequency of internal mammary metastases. The latter were present in the 15 per cent of tumours less than 3 cm in diameter and in the 61 per cent of tumours 8 cm or more in diameter. Out of the 156 cases with axillary invasion, 54 (41 %) had also internal mammary metastases. Out of the 148 cases without axillary invasion, 7 (4.7 %) had internal mammary metastases. Of the 165 patients operated upon until 1956 (by extrapleural exeresis not «en bloc » with the primary tumour), 91 (55.5 %) were alive after 5 years. The 5-year survival of cases with axillary metastases only was demonstated to be of the 52.4 per cent, whereas it drops to 13.2 per cent in cases with axillary and internal mammary metastases.