scholarly journals The Lymphatic System in Breast Cancer: Anatomical and Molecular Approaches

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1272
Author(s):  
Gianfranco Natale ◽  
Michael E. J. Stouthandel ◽  
Tom Van Hoof ◽  
Guido Bocci

Breast cancer is one of the most important causes of premature mortality among women and it is one of the most frequently diagnosed tumours worldwide. For this reason, routine screening for prevention and early diagnosis is important for the quality of life of patients. Breast cancer cells can enter blood and lymphatic capillaries, then metastasizing to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Rather than at the primary site, they seem to enter the systemic circulation mainly through the sentinel lymph node and the biopsy of this indicator can influence the axillary dissection during the surgical approach to the pathology. Furthermore, secondary lymphoedema is another important issue for women following breast cancer surgical treatment or radiotherapy. Considering these fundamental aspects, the present article aims to describe new methodological approaches to assess the anatomy of the lymphatic network in the axillary region, as well as the molecular and physiological control of lymphatic vessel function, in order to understand how the lymphatic system contributes to breast cancer disease. Due to their clinical implications, the understanding of the molecular mechanisms governing lymph node metastasis in breast cancer are also examined. Beyond the investigation of breast lymphatic networks and lymphatic molecular mechanisms, the discovery of new effective anti-lymphangiogenic drugs for future clinical settings appears essential to support any future development in the treatment of breast cancer.

2018 ◽  
Vol 5 (3) ◽  
pp. 8-16
Author(s):  
Yu. A. Dergunova ◽  
V. V. Podionov ◽  
V. K. Bozhenko ◽  
V. V. Kometova ◽  
M. V. Dardyk

Despite the sufficient amount of data accumulated in the literature, there are still no factors, on the basis of which it would be possible to estimate the regional lymph nodes status in breast cancer with a high degree of accuracy. The review presents literature data relating to the influence of clinicopathological, molecular-biological and genetic characteristics of primary tumor on lymph node metastases. Data of 66 foreign and Russian articles are included.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 571-571
Author(s):  
D. L. Ellsworth ◽  
R. E. Ellsworth ◽  
T. E. Becker ◽  
B. Deyarmin ◽  
H. L. Patney ◽  
...  

571 Background: Sentinel lymph node (SLN) biopsy status is a key prognostic factor for breast cancer patients. Sentinel nodes are believed to receive early disseminating cells from the primary tumor, but little is known about the origin of metastases colonizing the sentinel nodes. We used allelic imbalance (AI) to examine genomic relationships among metastases in the sentinel and non-sentinel axillary lymph nodes from complete axillary dissections in 15 patients with lymph node positive breast cancer. Methods: Sentinel nodes were localized by standard scintigraphic and gamma probe techniques using 1.0 mCi technetium-99m sulfur colloid. Pathologically positive nodes were identified by H&E histology and immunohistochemistry. Primary breast tumors and metastases in sentinel and axillary nodes were isolated by laser microdissection. AI was assessed at 26 chromosomal regions and used to examine the timing and molecular mechanisms of metastatic spread to the sentinel and axillary nodes. Results: Overall AI frequencies were significantly higher (p<0.05) in primary breast tumors compared to lymph node metastases. A high level of discordance was observed in patterns and frequencies of AI events between metastases in the sentinel and non-sentinel axillary nodes. Phylogenetic analyses showed that 1) multiple genetically-divergent lineages of metastatic cells independently colonize the lymph nodes; 2) some lymph node metastases appeared to acquire metastatic potential early in tumorigenesis, while other metastases evolved later; and 3) importantly, lineages colonizing the sentinel nodes appeared to originate at different times and to progress by different molecular mechanisms. Conclusions: Genomic diversity and timing of metastatic nodal spread may be important factors in determining outcomes of breast cancer patients. Metastases colonizing the sentinel nodes appear to arise at different times during disease progression and may not be descendants of progenitor cells that colonize the lymph nodes early in tumorigenesis. Metastatic growth in the sentinel nodes thus may be a consequence of stimulating factors from the primary tumor that affect proliferation of previously disseminated cells rather than the timing of metastatic spread. No significant financial relationships to disclose.


2019 ◽  
Author(s):  
Devon Livingston-Rosanoff ◽  
Sarah E. Tevis ◽  
Lee G. Wilke

Following treatment for breast cancer, disease can recur locally, regionally, or at distant sites. Locoregional recurrence is defined as recurrence in the ipsilateral breast, skin, chest wall, or regional lymph nodes. Concurrent metastatic disease is common in patients with locoregional recurrence; therefore, patients with recurrence should undergo a complete metastatic work-up. Isolated locoregional recurrence should be approached with curative intent, and patients should undergo resection and adjuvant therapy, as indicated, based on previous treatment and location of recurrence. Following treatment for locoregional recurrence, close monitoring should be performed, as patients are at an increased risk for developing metastatic disease. This review contains 5 figures, 1 table, and 50 references Key Words: breast cancer, CALOR clinical trial, locoregional recurrence, repeat radiation therapy, repeat sentinel lymph node mapping, adjuvant chemotherapy, repeat breast conserving therapy, mastectomy


2019 ◽  
Author(s):  
Devon Livingston-Rosanoff ◽  
Sarah E. Tevis ◽  
Lee G. Wilke

Following treatment for breast cancer, disease can recur locally, regionally, or at distant sites. Locoregional recurrence is defined as recurrence in the ipsilateral breast, skin, chest wall, or regional lymph nodes. Concurrent metastatic disease is common in patients with locoregional recurrence; therefore, patients with recurrence should undergo a complete metastatic work-up. Isolated locoregional recurrence should be approached with curative intent, and patients should undergo resection and adjuvant therapy, as indicated, based on previous treatment and location of recurrence. Following treatment for locoregional recurrence, close monitoring should be performed, as patients are at an increased risk for developing metastatic disease. This review contains 5 figures, 1 table, and 50 references Key Words: breast cancer, CALOR clinical trial, locoregional recurrence, repeat radiation therapy, repeat sentinel lymph node mapping, adjuvant chemotherapy, repeat breast conserving therapy, mastectomy


Breast Care ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. 173-175 ◽  
Author(s):  
Peter Niehoff ◽  
Silla Hey-Koch

Breast cancer treatment has undergone major changes in the last 20 years. Specifically, the role of axillary lymph node dissection has changed from radical axillary dissection with excision of a high number of lymph nodes to sentinel lymph node biopsy (SLNB). This paradigm shift is associated with a controversial debate regarding the significance of axillary staging, the need for surgery, and the role of radiotherapy. Looking ahead, lymph node staging and axillary treatment might shift from SLNB and/or axillary dissection to ultrasound-guided needle biopsy and irradiation of regional lymph nodes in order to reduce treatment-related sequelae in early-stage breast cancer.


2020 ◽  
Vol 22 (1) ◽  
pp. 46-52
Author(s):  
Irina V. Kolyadina ◽  
Tatiana Yu. Danzanova ◽  
Svetlana V. Khokhlova ◽  
Oksana P. Trofimova ◽  
Ekaterina V. Kovaleva ◽  
...  

The involvement of axillary lymph nodes is one of the most important prognostic factors, significantly affecting the treatment strategy for early breast cancer (BC). The risk of axillary lymph node metastases depends directly on a number of factors (age of women, size of tumor, presence of lymphovascular invasion and biological characteristics of cancer). The evaluation of regional lymph node status in patients with early BC includes the clinical examination of regional zones and the ultrasound study (US), using these methods can help to study lymph nodes shape, borders, margins and structure. The sensitivity of ultrasound in the evaluation of regional lymph nodes status directly depends on the biological subtype of the tumor; the minimum level of ultrasound sensitivity in the evaluation of lymph nodes status is detected for luminal HER2-negative cancer (less than 40%), and maximum sensitivity is detected for triple negative and HER2-positive subtypes (6871%). Clinical examination and modern ultrasound are the most accessible methods for the evaluation of regional lymph nodes status, but the possibility to misjudge metastatic process can be detected in 1/4 of patients. Verification of the diagnosis in the preoperative phase (fine-needle aspiration biopsy/core-needle biopsy under ultrasound guidance) allows minimize the number of errors for the regional staging. The sentinel lymph node biopsy (SLNB) is the gold standard of regional treatment in patients with early stage BC, nowadays. The randomized trials (NSABP B-32, ACOSOG q0011) show the safety of recession of performing regional lymph node dissection in favor of SLNB not only in case of clinically negative lymph nodes, but also in patients with metastases in 2 sentinel lymph nodes, upon condition that organ-conservative treatment and subsequent radiation therapy will be used. High-quality regional staging, the choice of the therapeutic algorithm in accordance with the biological characteristics of carcinoma, the application of the most effective modern drug regimes, the optimal radiation therapy allow not only minimize the extent of surgery, but also achieve high long-term survival results, provide excellent functional results and high quality of life in patients with the involvement of axillary lymph nodes.


2011 ◽  
Vol 2 (2) ◽  
pp. 101-112
Author(s):  
Mario Taffurelli

Axillary lymph node status is one of the most reliable prognostic factors of long-term survival in breast cancer surgery. Metastatic involvement of the axillary lymph nodes is also crucial in the decision making of potentially useful adjuvant treatment. Until the last decade, Axillary Lymph Nodes Dissection (ALND) was performed in order to obtain the regional lymphatic system staging. In case of non-metastatic spread, that kind of surgery was limited only to this purpose; no further oncological benefits were obtained and the patients were exposed to several comorbidities affecting this type of surgery. Complications after ALND are reported in 15-30% of cases. They are well known and range from early bleeding, infection, symptomatic nerve damage, and longstanding limb lymph-edema with an incredible impairment of the quality of life.The Sentinel Lymph Node (SLN) theory holds that the SLNs are the first nodes draining lymph from an anatomic region (i.e. the breast) where metastatic disease will most likely to be found. If that node is found to be cancer free, the entire lymphatic system is likely to be cancer free; if it is metastatic, there is an elevated chance of finding more metastatic nodes. Thanks to the application of this hypothesis, several patients over the last 10-15 years have avoided unnecessary major demolitive surgery. To obtain accurate evaluation of the SLN a multidisciplinary dedicated team is necessary. This procedure has been internationally validated and the false negative rate is nowadays less than 5% when performed by expert hands. Dedicated breast surgeons working in a high-volume centres are necessary to reach satisfactory confidence in performing this very specialised procedure in order to obtain an accurate staging. The number of women presenting to the breast oncology units is continuously increasing and the implementation of screening programs has been crucial in detecting numerous patients (more than 75%) with early disease and non-metastatic axillary lymph nodes. The practice of the SLN is clearly able to offer those patients an accurate staging with low comorbidities, preserving their quality of life.


Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Yuki Tany Hirakawa Vieira ◽  
Andre Luiz de Freitas Perina ◽  
Daniela Ferreira Vieira Vendramini ◽  
Thatyanne Cunha Esposito Gallo ◽  
Felipe Eduardo Martins Andrade

Introduction: Neuroendocrine tumor has an annual incidence of 2–5 cases/100,000 inhabitants, most of them asymptomatic, and may clinically present as carcinoid syndrome: facial flushing, diarrhea, and bronchospasm. It has a great tendency to metastasize to regional lymph nodes and liver, being unusual in the breast. Clinical case: A black 47-year-old woman without comorbidities presented a nodule with progressive growth for 2 years in the right upper inner quadrant (RUIQ), biopsied and diagnosed as breast cancer, without a specific subtype or immunohistochemistry (IHC). Physical examination revealed a 3 cm nodule, hard and fixed axillary lymph node, and enlarged yet fibroelastic and mobile anterior cervical lymph node. Ultrasound (US) identified two irregular nodules in the RUIQ and the junction of the right outer quadrants (JROQ) measuring 2.5 cm and 0.7 cm, respectively, and level I axillary lymph node with cortical thickening. The JROQ nodule and the axillary lymph node were biopsied. The cervical lymph node did not show loss of hilum or suspicious abnormalities on US and was not biopsied. Anatomopathological results of the nodule were compatible with invasive carcinoma without a specific subtype, with estrogen receptor weakly positive (10%), Ki-67 7%, and negative for other markers. The axillary lymph node was negative for metastasis. During staging, an abdominal computed tomography identified a 1.9 cm lesion of likely neuroendocrine origin in the ileocecal valve with metastasis to the liver, regional lymph nodes, and breast. Complementary IHC of the biopsy slide was later performed with chromogranin, synaptophysin, and CDX-2, and the diagnosis reached was breast metastasis of neuroendocrine tumor. An external review of biopsy slides of the RUIQ nodule was requested, and the patient was referred to the oncology department to continue treatment. Conclusion: Metastasis of gastrointestinal tumors to the breast corresponds to less than 0.5% of cancers, with 15 reports in the literature, of which only 7 were asymptomatic, and their clinical presentation started with breast lesion, as in the case described herein. Given its rarity, as well as the clinical and radiological difficulties in differentiating these lesions, special attention must be paid to differential diagnoses, especially in cases of discrepancies between the tumor histology and IHC or lack of correlation between image and clinical condition.


2021 ◽  
Vol 17 (3) ◽  
pp. 24-36
Author(s):  
V. V. Rodionov ◽  
O. V. Burmenskaya ◽  
V. V. Kometova ◽  
D. Yu. Trofimov ◽  
M. V. Rodionova ◽  
...  

Objective: to identify molecular genetic predictors of metastatic spread to regional lymph nodes in patients with breast cancer (BC) based on the analysis of gene expression profile of the primary tumor.Materials and methods. The study included 358 patients with BC who underwent surgical treatment in breast cancer department of Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. Among all included into the study patients, 132 (36.9 %) had metastases in at least one axillary lymph node. Molecular genetic examination of the tumor tissue was carried out using reverse transcription polymerase chain reaction; the diagnostic panel consisted of 45 functional and 3 reference genes. Results. Patients with metastases to regional lymph nodes were generally younger (p = 0.006), had larger primary tumor (p<0.001) and higher total malignancy score (p<0.001). The groups were also significantly different in tumor location (p = 0.005). Comparative analysis of transcriptome tumor profiling revealed statistically significant differences between groups in the level of expression of three genes: TMEM45A (p = 0.016), CCND1 (p = 0.019), and MIA (p = 0.046). Based on the data obtained we used mathematical modeling and created a predictive model, which with a high degree of probability (AUC = 0.791) allowed to predict the presence of regional lymph nodes metastases in patients with BC.Conclusion. TMEM45A, CCND1 and MIA gene expression in the primary tumor were the markers of lymph node involvement in BC. The developed predictive genetic signature can become an additional diagnostic tool to predict the risk of lymph node metastases at the point of planning the volume of axillary surgery in patients with BC.


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