Do cytokeratin-positive-only sentinel lymph nodes warrant complete axillary lymph node dissection in patients with invasive breast cancer?

The small number of nodes harvested with lymphatic mapping and sentinel lymph node (SLN) biopsy has allowed a more detailed pathologic examination of those nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an attempt to minimize the false negative rate for SLN mapping. This study examines the value of CK-IHC positivity in predicting further lymph node involvement in the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and SLN biopsies were performed for invasive breast cancer. SLNs were examined by imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence of metastatic disease by any of the above techniques were eligible for complete axillary node dissection (CAND). The frequency with which these modalities predicted further lymph node involvement in the axillary basin was compared. Of the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN. Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty-six of the CK-IHC-positive-only patients underwent CAND. Three of these 26 patients (11.5%) had additional metastases identified after CAND. The sensitivity levels with which each modality detected further axillary lymph node involvement were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87 per cent. A logistic regression to compare the prognostic value of the three modalities was performed. All were significant, with odds ratios of 19.1 for CK-IHC (P = 0.015), 5.3 for H&E (P = 0.033), and 3.86 for imprint cytology (P = 0.0059). These data validate the enhanced detection of CK-IHC for the evaluation of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients with invasive breast cancer. However, the therapeutic value of CAND or adjuvant therapies based on CK-IHC-positive SLNs would be best answered by prospective randomized trials.     

Is axillary lymph node dissection always necessary in breast cancer patients with a positive sentinel node?

Axillary lymph node dissection (ALND) is recommended for patients with breast cancer metastasis to a sentinel lymph node (SLN). However in 40-70% of cases, the SLN may be the only area of metastasis in the dissected axillary contents. In patients with a positive SLN, independently predictive factors for non-SLN metastasis include size of the primary tumor, the size of the SLN metastases, extracapsular extension, and the proportion of positive SLN's among all identified SLNs. Some authors have developed scores and nomograms to estimate a patient's risk for non-SLN metastases. These scores and nomograms should be applied prospectively to a large numper of SLN positive patients who thereafter undergo completion ALND. It is necessary to verify the predictive validity of these scores before we recommend the abandonment of ALND in patients with a very low likelihood of non-SLN metastasis. In this article we review the various predictive factors of non-SLN involvement and the scores or nomograms which have been developed to predict the likelihood of a positive ALND after a positive SLN biopsy.     

Can axillary lymph node dissection be omitted in patients with breast cancer and positive sentinel nodes?

Sentinel lymph node biopsy has evolved as the surgical procedure of choice for women with clinically negative axillae, as part of an effort to move toward the less invasive surgical management of breast cancer. Axillary lymph node dissection remains the standard of care for patients with a positive axillary node and was previously performed on all patients with breast cancer prior to the implementation of the sentinel lymph node biopsy. There is, however, controversy regarding whether or not all patients with a positive sentinel lymph node need to undergo completion axillary dissection for either prognostic or therapeutic purposes. This article reviews the literature related to this controversial and evolving topic.     

What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma in situ?

BACKGROUND: Some surgeons have advocated sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS). The value of the information obtained is not clear. METHODS: From 1972 to 2005, 564 selected patients with pure DCIS had axillary staging with either SNB or axillary lymph node dissection (ALND). Data were collected in a prospective database. RESULTS: Only 2 of 564 patients had positive nodes by hematoxylin and eosin, and they were both in the ALND group. Both patients had mastectomies, were upstaged, received chemotherapy, and survived for more than 10 years without local or distant recurrence. Among 171 patients who had SNB, 10 had isolated tumor cells found by immunohistochemistry. Two patients who underwent SNB had local recurrence, neither developed distant or regional recurrence. Six of 564 patients in the ALND group developed local invasive recurrence and died of metastatic breast cancer, but none of them had positive nodes. CONCLUSIONS: Information from lymph node examination in DCIS patients failed to predict poor outcome. SNB is useful for DCIS in mastectomy, especially with immediate reconstruction. It may be indicated for DCIS at high risk for upgrading to invasive cancer on final excision, but reliable criteria for identifying these tumors are not yet available.     

Positive axillary sentinel lymph node: is axillary dissection always necessary?

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when axillary involvement is minimal (micrometastases or isolated tumor cells). In fact, clinical practice has run ahead of the evidence, since recent population-based data indicate that AD is 'underused' in breast cancer patients when the SN is positive. Several trials are addressing the problem (IBCSG 23-01, ASCOG Z0011, EORTC AMAROS). Only Z0011 has published interim results, finding, after a median follow-up of 6.3 years, no differences in locoregional recurrence or regional recurrence between patients, with a positive SN, who received AD vs. no further axillary treatment. Our own retrospective study evaluated patients with micrometastases or isolated tumor cells in the SN who received no further axillary treatment. We found high five-year survival and low cumulative incidence of axillary recurrence, supporting the findings of Z0011 and justifying the increasingly common practice of foregoing AD in women with minimal SN involvement. It is important to sound a note of caution however: If axillary dissection is not always necessary in women with a positive axilla, it seems important to be able to reliably identify the patients at high risk of developing overt axillary disease who should receive elective AD. Ancillary analyses of the IBCSG 23-01 and AMAROS trials, still in follow-up, may be able to do this.     

Can radiotherapy replace axillary dissection for patients with positive sentinel nodes?

The substitution of sentinel node biopsy for axillary dissection for patients with early-stage breast cancer has reduced the morbidity of pathologic axillary nodal staging substantially. However, this has resulted in substantial controversy about how to manage patients with positive sentinel nodes. Radiation therapy has been used for many years instead of or in addition to axillary sampling or axillary dissection. This article will examine parts of this experience relevant to the treatment of patients with positive sentinel node biopsy, the limited data on outcome of patients with a positive sentinel node biopsy who do not undergo completion dissection, and the toxicities of axillary irradiation. Finally, I suggest an overall approach to the management of patients with a positive sentinel node biopsy.     

Is sentinel lymph node biopsy more accurate than axillary dissection for staging nodal involvement in breast cancer patients?

Today evaluation of axillary involvement can be routinely performed with the technique of sentinel lymph node biopsy (SLNB). One of the greatest advantages of SLNB is the nearly total absence of local postoperative complications. It is important to understand whether SLNB is better than axillary lymph-node dissection (ALND) for staging axillary nodal involvement. The aim of the study was to evaluate the axillary staging accuracy comparing three different methods: axillary dissection, sentinel node biopsy with the traditional 4-6 sections and sentinel node biopsy with complete analysis of the lymph node. 527 consecutive patients (525 females and 2 males) with invasive breast cancer < or = 3 cm and clinically negative axillary nodes were divided into 3 different groups: group A treated with axillary dissection, group B treated with sentinel nodal biopsy analysed with 4-6 sections, and group C treated with sentinel node biopsy with analysis of the entire node. All patients underwent a quadrantectomy to treat the tumor. Group differences and statistical significance were assessed by ANOVA. The percentages of N+ in group A and group B were 25.80% and 28% respectively, while in the third group it rose to 45%, or almost half the patients. The differences among the three groups were statistically significant (p = 0.02). From our analysis of the data it emerges that axillary dissection and sentinel node biopsy with analysis of 4-6 sections have the same accuracy in staging the nodal status of the axilla; analysis of the entire sentinel lymph node revealed an increased number of patients with axillary nodal involvement, proving more powerful in predicting nodal stage. SLNB with complete examination of the SLN removed can be considered the best method for axillary staging in breast cancer patients with clinical negative nodes. In our study, the percentage of metastases encountered after complete examination of SLN was 45% compared to the accuracy of axillary dissection that was only 25.8%. Moreover, this approach avoids the useless axillary cleaning in about 55-60% of cases, decreasing postoperative morbidity and mortality.     

Do bone marrow micrometastases correlate with sentinel lymph node metastases in breast cancer patients?

BACKGROUND: Sentinel lymph node biopsies (SLNB) are used to detect axillary metastases as an important prognostic indicator for breast cancer patients. Bone marrow micrometastases (BMM) have also been shown to predict prognosis. This study examines whether SLNB and BMM are associated. STUDY DESIGN: A retrospective analysis was performed on 124 stages I to III breast cancer patients treated with mastectomy or lumpectomy, SLNB, and bone marrow aspiration between 1997 and 2003. SLNB were examined for the presence of metastases by hematoxylin and eosin (H&E) stains and also by immunohistochemistry (IHC) for lymph nodes negative by H&E. The kappa statistic was used to evaluate the association (agreement) between SLNB and BMM. RESULTS: In this study population, 36 patients (29%) had micrometastases detected in their bone marrow, and 51 patients (41%) had positive sentinel lymph nodes. Of the patients with positive BMM (n = 36), 53% (19 of 36) had positive SLNB (14 of 19 by H&E and 5 of 19 by IHC). In patients with negative BMM (n = 88), 36% (32 of 88) had a positive SLNB (27 of 32 by H&E and 5 of 32 by IHC). The kappa statistic and associated 95% confidence interval indicated poor agreement between SLNB and BMM (kappa = 0.15; 95% CI = -0.03, 0.32). CONCLUSIONS: There was poor agreement between axillary metastases and micrometastases detected in the bone marrow. This study suggests that BMM and axillary metastases are not concordant findings in most patients.     

Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients

BACKGROUND

The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial.

Methods

A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR).

Results

Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06).

Conclusions

SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.     

Do all lupus patients need statins?

Statin therapy decreases cardiovascular morbidity and mortality rates when used as either primary or secondary prevention. An immunomodulating effect of statins has been suggested. Incontrovertible evidence of accelerated atheroma has been obtained in patients with systemic lupus erythematosus (SLE). Routine statin therapy in SLE patients might therefore produce both cardiovascular and immunological benefits. However, routine statin therapy is inappropriate in SLE patients, the main reason being the absence of a vast interventional study done specifically in this population. An immunomodulating role for statins in SLE has not been convincingly established. The effect of statin therapy on markers for subclinical atheroma (intima-media thickness changes over time) is unclear, and there are no studies proving that statins are effective when used for primary or secondary cardiovascular prevention. Nevertheless, we believe that a serum lipid profile should be obtained once a year in all SLE patients. There is a sound rationale for classifying all SLE patients as being at high cardiovascular risk and those receiving secondary prevention as at very high risk. Consequently, the serum LDL-cholesterol level must be kept below 100 mg/dL and 70 mg/dL in these two populations, respectively. Statins are the only widely recommended drugs for achieving these treatment targets. Statin therapy requires specific monitoring precautions (transaminase levels) given the high prevalence of comorbidities and use of concomitant medications in SLE patients.     

Is a completion axillary dissection indicated for micrometastases in the sentinel lymph node?

OBJECTIVE: The purpose of this study is to determine if a completion axillary dissection (CAD) is necessary when microscopic metastasis (<2 mm) is detected in the sentinel lymph node (SLN) of patients diagnosed with breast cancer. METHODS: A retrospective chart review was performed on 227 consecutive breast cancer patients who underwent SLN mapping (SLNM) between June 1998 and March 2001. These patients underwent intraoperative lymphatic mapping with peritumoral injections of blue dye alone or in combination with technetium-labeled sulfur colloid. The SLN was assessed by touch preparation or frozen section at the time of surgery, and later, by hematoxylin and eosin stain. Patients in whom the SLN showed evidence of metastatic disease on frozen section underwent immediate CAD. RESULTS: One patient was excluded because of inability to identify the SLN. Of the 226 patients in whom SLNM was successful, 67 (27%) had macrometastasis in the SLN, and a completion CAD was performed. Thirty-four of these 67 patients (51%) had additional disease in the axilla. A total of 15 patients (6.7%) was determined to have micrometastasis. In 11 patients, micrometastasis was identified and CAD was performed with no further evidence of disease. The 4 patients diagnosed with micrometastatic disease on permanent staining did not have further surgical intervention. The 15 patients identified with micrometastasis show no evidence of local recurrence to date, with a mean follow-up of 13.5 months (range 1 to 27). CONCLUSIONS: This study suggests that CAD may not be necessary for the subset of breast cancer patients with micrometastasis detected upon SLNM. A larger randomized prospective study with long-term follow up is necessary to confirm these data.     

Does the presence of sentinel lymph node macrometastases in breast cancer patients require axillary lymph node dissection?—Single‐center analysis

According to the current guidelines on treatment of breast cancer patients, identification of metastases in the sentinel lymph node (SLN (+)) is not an absolute indication for necessary axillary lymph node dissection (ALND). In our study, we present long‐term outcomes of treatment among SLN(+) patients referred for conservative treatment, for example, no further ALND. A total of 3145 breast cancer patients subjected to sentinel lymph node biopsy (SLNB) between November 2008 and June 2015. SLN metastases were identified in 719 patients (22.9%). Locoregional recurrences and distant metastases as endpoints were distinquished. The mean follow‐up time for patients after ALND was 36.2 months (6‐74 months); 18.8 months (6‐38 months) for patients with SLN macrometastases without ALND; and 34.0 months (6‐74 months) for patients with micrometastases. Adjuvant ALND was performed in 626 of SLN(+) patients. Conservative treatment was applied in the remaining 93 cases. Among SLN(+) patients without adjuvant ALND, there was one case of recurrence (1.07%). In the group of patients without SLN, metastases recurrence was noted in 32 patients (1.32%). Among SLN(+) patients diagnosed with macrometastases, recurrence concerned 2.01% of analyzed cases (all subjected to ALND). Lack of radical surgical treatment in SLN(+) breast cancer patients did not lead to worsening long‐term outcomes. In the occurrence of macrometastases to the sentinel lymph node, abandoning completion axillary lymph node dissection might be a reasonable option. However, it would require continuation of current research, preferably involving a clinical trial.     

Is complete axillary lymph node dissection neccessary in T1 stage invasive pure tubular carcinomas of the breast?

The purpose of this study was to evaluate the frequency of axillary lymph node metastasis in invasive pure (not mixed) tubular carcinomas of the breast and to compare our results to other series published in the literature. We analyzed 16 cases of pure tubular carcinoma measuring 2 cm or less in diameter from our database from 1988 to 2004 diagnosed in lumpectomy and mastectomy specimens with associated axillary lymph node dissection. Histopathologic features were reviewed in all patients. In all cases, no axillary lymph node metastasis was observed (0%). These data slightly differ from the results of some studies recently published in the literature, in which the overall nodal involvement in pure tubular carcinomas ranges from 0% to 20%. We conclude that in invasive pure tubular carcinomas of the breast measuring less than 2 cm in diameter, complete axillary lymph node dissection should be avoided, and we propose a sentinel lymph node analysis instead.