Variability of the depth of supraclavicular and axillary lymph nodes in patients with breast cancer: is a posterior axillary boost field necessary?

PURPOSE: To determine the variability of the depth of supraclavicular (SC) and axillary (AX) lymph nodes in patients undergoing radiation therapy for breast cancer and to relate this variability with the patient's anterior/posterior (A/P) diameter. The dosimetric consequences of the variability in depth are explored and related to the need for a posterior axillary boost field. METHOD AND MATERIALS: In 49 patients undergoing treatment-planning computed tomography (CT) scanning in the treatment position, the maximum depth of the SC and AX lymph nodes was measured on CT images. The A/P diameter was measured at the location of the SC and AX, respectively. The relationship between the SC/AX lymph node depth and patient diameter was determined using linear regression. For an anterior SC and AX field, the relative dose to the SC and AX lymph nodes were calculated for a 6 MV photon beam. RESULTS: The maximum depth of the SC lymph nodes ranged from 2.4 to 9.5 cm (median, 4.3 cm). The depth was less than 3 cm in 4 patients, 3-6 cm in 39 (80%), and greater than 6 cm in 6 patients. There was a linear relationship between the SC lymph node depth and the A/P diameter. The depth of the SC lymph nodes in cm equals approximately one-half of the A/P diameter minus 3.5 (r(2) = 0.69). In 94% (46 of 49) of patients, the SC lymph node depth was between one-fifth and one-half of the A/P diameter.The depth of the axillary lymph nodes ranged from 1.4 to 8 cm (median, 4.3 cm). The depth was less than 3 cm in 8 patients, 3-6 cm in 32 (65%), and greater than 6 cm in 9 patients. The AX lymph node depth in cm equals approximately one-half of the A/P diameter minus 3 (r(2) = 0.81). In all patients, the AX lymph nodes were shallower than mid-depth.The depth of the SC and AX lymph nodes was within +/- 1 cm in 53% (26 of 49) of patients. The AX lymph nodes were located at >/= 1 cm shallower or greater depth than the SC in 24.5% (12 of 49) and 22.5% (11 of 49) of patients, respectively. If an anterior 6-MV beam only is used to treat the SC and AX lymph nodes in these 49 patients, the dose to the AX is within +/- 5% of the SC dose in 53% (26 of 49) patients and is 90% or more of the dose delivered in the SC in 90% (44 of 49) of patients. CONCLUSION: The maximum depth of the SC and AX lymph nodes varies widely and is related to the patient's size represented by the A/P diameter. In most patients, the AX lymph nodes lie at approximately the same depth or shallower than the SC. Therefore, the rationale for a posterior axillary boost field needs to be further assessed. When the AX and SC lymph nodes are deep, opposed supraclavicular and axillary fields and/or the use of a higher energy beam might be reasonable.     

Mammographic density as a marker of breast cancer risk?

Mammographic density is a strong, independent risk factor for breast cancer. Women with high mammographic density have a fourfold increased risk for breast cancer compared with women with low density. Because age and obesity are the strongest predictors of mammographic density, it is important to adjust for them in risk analyses. In randomized trials, tamoxifen decreased risk for breast cancer and also decreased mammographic density. Combined estrogen plus progestin therapy increased mammographic density. Density is a strong risk factor in low-risk groups (Asian women) and high-risk groups (BRCA mutation carriers). Several risk assessment tools now incorporate mammographic density, including an updated Gail model, though these models require additional validation before they should be used widely. Improvements in density measurements may allow risk assessment to occur routinely with mammography and improve targeting of breast cancer prevention efforts.     

Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?

PURPOSE: The elective treatment of internal mammary lymph nodes (++IMNs) in breast cancer is controversial. Previous randomized trials have not shown a benefit to the extended radical mastectomy or elective IMN irradiation overall, but a survival benefit has been suggested by some for subgroups of patients with medial tumors and positive axillary lymph nodes. The advent of effective systemic chemotherapy and potential for serious cardiac morbidity have also been factors leading to the decreased use of IMN irradiation during the past decade. The recent publishing of positive trials testing postmastectomy radiation that had included regional IMN irradiation has renewed interest in their elective treatment. The purpose of this study is to critically review historical and new data regarding IMNs in breast cancer. METHODS AND MATERIALS: The historical incidence of occult IMN positivity in operable breast cancer is reviewed, and the new information provided by sentinel lymph node studies also discussed. The results of published randomized prospective trials testing the value of elective IMN dissection and/or radiation are analyzed. The data regarding patterns of failure following elective IMN treatment is studied to determine its impact on local-regional control, distant metastases, and survival. A conclusion is drawn regarding the merits of elective IMN treatment based on this review of the literature. RESULTS: Although controversial, the existing data from prospective, randomized trials of IMN treatment do not seem to support their elective dissection or irradiation. While it has not been shown to contribute to a survival benefit, the IMN irradiation increases the risk of cardiac toxicity that has effaced the value of radiation of the chest wall in reducing breast cancer deaths in previous randomized studies and meta-analyses. Sentinel lymph node mapping provides an opportunity to further evaluate the IMN chain in early stage breast cancer. Biopsy of "hot" nodes may be considered in the future to select patients who are most likely to benefit from additional regional therapy to these nodes. CONCLUSIONS: Irradiation of the IMN chain in conjunction with the chest wall and supraclavicular region should be considered only for those with pathologically proven IMNs with the goal of improving tumor regional control.     

Assessing the status of axillary sentinel lymph nodes of breast carcinoma patients by a real-time quantitative RT-PCR assay for mammaglobin 1 mRNA

Summary The aim of the study was to assess the accuracy of a real-time quantitative RT-PCR (qRT-PCR) assay for mammaglobin 1 mRNA in the detection of metastatic breast cancer in axillary sentinel lymph nodes (SLN), comparing the results with those of qualitative RT-PCR assays and of an extensive histopathological examination. A retrospective series of 81 SLN from 72 patients and a validation series of 61 SLN from 61 patients were evaluated. In the retrospective series, the qRT-PCR assay was positive for 23 (28.4%) of the 81 SLN. The overall concordance with histopathology was 93.8%, with a sensitivity of 90.9%, a specificity of 94.9%, a positive predictive value (PPV) of 87% and a negative predictive value (NPV) of 96.6%. In the same series, qualitative RT-PCR showed an overall concordance with histopathology of 86.4%, a sensitivity of 72.7%, a specificity of 91.5%, a PPV of 76.2% and a NPV of 90%. In the validation series, including 23 patients with pure in situ carcinoma, the real-time qRT-PCR assay showed an overall concordance with the histopathologic findings of 93.4%, with a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 50.0% and a NPV of 98.2%. We conclude that real-time qRT-PCR assays for mammaglobin 1 are more sensitive and specific that qualitative RT-PCR assays for the detection of metastatic breast carcinoma in axillary SLN, but it should not be regarded as a possible substitute for an extensive histopathological scrutiny of the SLN in the clinical practice.     

Is there a need for axillary dissection in breast cancer?

The involvement of axillary nodes remains a significant prognostic factor in breast cancer. However, management has changed from complete surgical staging to sentinel lymph node biopsies. Although little controversy exists regarding patients with negative sentinel lymph node biopsies, some remains regarding what to do with patients with small volume of axillary disease. This article focuses on the examination of recent evidence in management of the axilla. It focuses on both the prognostic and therapeutic information gleaned from isolated tumor cells and micrometastatic disease and on the use of completion axillary lymph node dissections or axillary radiation in preventing regional recurrence.     

Contrast‐enhanced computed tomography detection of occult breast cancers presenting as axillary masses

Some nonpalpable breast cancers presenting as axillary metastases (occult breast cancer, OBC) are not clinically detectable by either mammography (MMG) or ultrasonography (US). We performed contrastenhanced computed tomography (CECT) in order to locate the primary tumors in five cases of OBC and succeeded in locating all of them.     

Does increased tumor burden of sentinel nodes in breast cancer affect detection procedure?

Numerous studies have shown that sentinel lymph node biopsy (SLN) has a high level of detection sensitivity. Successful detection procedure depends on the amount of radioactivity and accumulation of blue dye in the SN. Our aim was to relate the differences observed in intraoperative SN presentation to tumor burden, characteristics of the primary tumor and patient attributes.     

A place for fiber diffraction in the detection of breast cancer?

AIMS: To review the potential relevance and the place that a particular change in the fiber diffraction of hair might have in the future management of breast cancer and other pathologies. METHOD: A comprehensive overview was obtained using a complete search of the Australian National University Library (data range) and Medline (data range) using the search terms "review breast cancer screening/diagnosis/detection" and "X-ray diffraction of hair". Publications in the past 5 years were selected but older reports that were commonly referenced were not excluded. RESULTS: To date, our results have demonstrated that a specific change occurs in the diffraction pattern of hair for persons with breast cancer. Further research has shown that this change is present in the hair at an earlier stage of the cancer growth than is detectable by mammography. In addition, the change has been found to disappear when the cancer has been successfully removed. DISCUSSION/CONCLUSION: This technology uses only a few hairs, is totally user-friendly, non-invasive and does not require the patient to be exposed to any radiation. As a low-risk procedure, it could potentially provide a much needed, cost-effective early screening test for the presence of breast cancer in women of any age. As the patients are not required to be present during the test, it could also provide a testing service for women in remote areas. In this review, the origin of the diffraction pattern and the diagnostic information that can be gleaned from it are outlined.     

Is intraoperative touch imprint cytology of sentinel lymph nodes in patients with breast cancer cost effective?

BACKGROUND: Sentinel lymph nodes (SLNs) are generally evaluated postoperatively, requiring 5-7 days for assessment. SLNs can also be evaluated intraoperatively by using touch imprint cytology (TIC), thus providing the surgeon immediate feedback and allowing for concurrent completion node dissection (CND) for positive SLNs. The authors hypothesized that TIC, when compared with standard postoperative SLN assessment alone, would permit a cost-effective evaluation of SLNs in patients with clinically node-negative breast cancer. METHODS: A decision-analysis model was created to compare TIC with standard postoperative SLN assessment alone. Sensitivity and specificity of TIC were determined prospectively from 342 patients who underwent SLN biopsy assessed by both techniques. Short-term health states associated with surgical staging were defined, and utilities were estimated using EuroQol-5D. Base-case analysis was performed to estimate quality-adjusted life years and the incremental cost-effectiveness ratio. Sensitivity analyses were performed to examine stability of model parameters. RESULTS: For each tumor stage, TIC was cost effective, and for patients with larger tumors (T3 and T4), TIC was the dominant strategy. The analysis was robust to changes in sensitivity and specificity of TIC, prevalence of metastasis, probability of complications, and cost. However, when utility associated with standard SLN assessment was 0.9 or greater, this became the preferred strategy. CONCLUSIONS: TIC is cost effective for assessing SLN metastasis intraoperatively. For patients with larger tumors, it is not only more effective, but also less costly than standard SLN assessment alone. TIC may be particularly useful for patients who experience significant anxiety while awaiting results of standard SLN assessment.     

Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1–3 lymph node metastases

Background

Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer.

Methods

From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS).

Results

Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037).

Conclusion

Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1–3 metastatic lymph nodes.     

Does the subtype of breast cancer affect the diagnostic performance of axillary ultrasound for nodal staging in breast cancer patients?

IntroductionImaging findings can be affected by histopathological characteristics, such as breast cancer subtypes. The aim was to determine whether the diagnostic performance, in particular negative predictive value (NPV), of axillary US differs per subtype of breast cancer.MethodsAll patients diagnosed between 2008 and 2016 in our hospital with primary invasive breast cancer and an axillary US prior to axillary surgery were included. Histopathology of axillary surgery specimens served as gold standard. The NPV, sensitivity, specificity, positive predictive value (PPV) and accuracy of the axillary US were determined for the overall population and for each subtype (ER+/PR+HER2-,HER2+, triple negative tumors). The Chi-square test was used to determine the difference in diagnostic performance parameters between the subtypes.ResultsA total of 1094 breast cancer patients were included. Of these, 35 were diagnosed with bilateral breast cancer, resulting in 1129 cancer cases. Most common subtype was ER+/PR+HER2- in 858 cases (76.0%), followed by 150 cases of HER2+ tumors (13.3%) and 121 cases of triple negative tumors (10.7%). Sensitivity, specificity and accuracy of axillary US did not significantly differ between the subtypes. There was a significant difference for NPV between triple negative tumors and HER2+ tumors (90.3% vs. 80.2%, p = 0.05) and between HER2+ and ER/PR+HER2- tumors (80.2% vs. 87.2%, p = 0.04).ConclusionThere was no significant difference in the diagnostic performance of axillary US between the subtypes, except for NPV. This was highest in triple negative subtype and lowest in HER2+ tumors. This can be explained by the difference in prevalence of axillary lymph node metastases in our cohort.