Will early detection of non-axillary sentinel nodes affect treatment decisions?

Axillary lymph node involvement is the best prognostic factor for breast cancer survival. Staging breast cancers by axillary dissection remains standard management and is part of the UK national guidelines for breast cancer treatment. In the presence of involved axillary lymph nodes best treatment has been shown to be axillary clearance (Fentiman and Mansell, 1991), but clearly for women whose nodes are uninvolved avoidance of morbidity is optimal and this will be achieved by minimal dissection of the axilla. Thus, for node-negative women the introduction of the sentinel node biopsy technique may revolutionise the approach to the axilla. These will be women with mammographic screen detected small well and moderately differentiated tumours (Hadjiloucas and Bundred, 2000). The impact of sentinel node biopsy in women who have symptomatic large tumours is unproven, and around half of these women will require a second procedure to clear their axilla or radiotherapy as treatment. Even for those women found to have involved sentinel lymph nodes the ability to use early systemic chemotherapy followed by axillary clearance or radiotherapy may provide long-term survival gains. Sentinel node biopsy should not, however, become routine practice until randomised controlled trials have proven its benefit and safety in reducing morbidity. Several randomised controlled trials (including ALMANAC) are currently underway.     

Survival and recurrences five years after selective treatment for breast carcinoma.

110 consecutively diagnosed breast-cancer patients in all stages were included in a study to evaluate a selective surgical and radiotherapeutical treatment. The surgical treatment was total mastectomy and exploration of the axilla, with lymphnode biopsy and peroperative cytological examination. Axillary dissection was done only when this examination showed metastases. No radiotherapy was given to the axilla in patients with lateral cancers in the absence of metastases, or with limited metastasization (no periglandular growth, no growth in apical nodes). In medial and central cancers, radiotherapy was applied to the parasternal and supraclavicular nodes irrespective of axillary involvement. A staging system with a combined clinical and histopathological classification was used and formed the basis for the selective treatment. The corrected 5-year survival for the whole material was 80%, for those without axillary metastasis (Stage I) 95% and for those with axillary metastasis (Stage II) 68%. Six women were alive with known distant metastases. Of 63 patients without identified axillary metastases at the time of surgery, axillary recurrences occurred in only 3 (5%). It was concluded that patients without axillary metastases can be reliably selected by the peroperative examination used, and that in this group simple mastectomy results in a high disease-free survival. Early diagnosis and a possible beneficial effect of the actual therapeutic programme might both have contributed to the high overall survival.     

Axillary node dissection for early breast cancer: some is good, but all is better.

Optimal management of the axillary lymphatics in breast cancer patients remains a contentious subject. Axillary recurrence, while infrequent, may have very significant clinical consequences in the affected patient. Axillary sampling, partial and total axillary lymphadenectomy, radiotherapy, and surgery plus radiotherapy are discussed with attention to efficacy in prevention of axillary recurrence, accuracy of nodal staging, and morbidity. The incidence of axillary recurrence decreases and accuracy of staging increases with the number of lymph nodes resected. There is little difference in incidence of morbidity between partial and total axillary lymphadenectomy. Radiotherapy is not as effective as lymphadenectomy for regional disease control and, when administered following a surgical staging procedure, increases the risk of lymphedema of the ipsilateral upper extremity and, in patients undergoing breast-conserving surgery, the ipsilateral breast. We believe that total axillary lymphadenectomy provides optimal regional disease control and axillary staging with morbidity comparable to that of partial lymphadenectomy.     

Does radical surgery to the axilla give a survival advantage in more severe breast cancer?

There is some evidence that more radical treatment of the axilla may improve survival in node-positive disease, but there are concerns about the resultant morbidity from axillary surgery and radiotherapy. The aim of this study was to compare the outcome of axillary node clearance with axillary sampling in similar patients by comparing loco-regional recurrence and overall survival. Patients with invasive breast cancer undergoing axillary surgery between 1986 and 1997 were included. The axillary procedure performed in these patients was either an axillary sample or a level III axillary clearance. To compare like with, the patients were separated into good, moderate and poor prognostic groups by the Nottingham Prognostic Index (NPI) and overall survival was compared by a Kaplan-Meier life table analysis and the log rank test. 734 consecutive patients with operable invasive breast cancer were treated by axillary clearance n=350 or sampling n=384. The mean follow-up in the clearance group was 65 months versus 66 months in the sampled group. Local recurrence in the clearance group was 11% versus 6% in the sampled group, regional recurrence 2% versus 3% and distant metastasis 28% versus 13%. Kaplan-Meier analysis of the three prognostic groups for the clearance versus sampled groups showed no differences in the absolute survival (log rank: P=0.3, P=0.8 and P=0.6 for the good, moderate and poor prognostic groups, respectively). A conservative surgical approach to the axilla did not significantly increase the incidence of local or regional recurrence and the expected survival benefit from a radical axillary clearance was not apparent.     

The diagnosis and management of pre-invasive breast disease Problems associated with management of pre-invasive lesions

The treatment of ductal carcinoma in situ (DCIS) involves adequate surgical excision with adjuvant radiotherapy where appropriate. An inadequate excision margin and young age are independent risk factors for local recurrence. Routine surgery to axillary lymph nodes is not recommended in pure DCIS. In localised DCIS, adjuvant radiotherapy is recommended on the basis of tumour size, margin width and pathological subtypes. The role of adjuvant tamoxifen as systemic therapy is controversial. The treatment of atypical ductal/lobular hyperplasia and lobular carcinoma in situ involves surgical excision to exclude coexisting DCIS or invasive disease.     

Radiothérapie axillaire prophylactique des cancers du sein

Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk–benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy.     

Safety and feasibility of breast conserving therapy in Indian women: two decades of experience at Tata Memorial Hospital

PURPOSE: The NIH consensus statement on the management of breast cancer has highlighted the paucity of outcome data in non-Caucasian women. Treatment outcome and factors determining it in a large cohort of ethnic Indian women treated with breast conserving therapy (BCT) at Tata Memorial Hospital are reported here. MATERIALS AND METHODS: During 1980-2000, 1,022 pathological Stage I/II breast cancer patients (median age 43 years) underwent BCT (wide excision, complete axillary clearance, whole breast radiotherapy with 6 MV photons plus tumor bed boost, +/-systemic therapy). Median pathological tumor size was 3 cm (1-5 cm). Axillary node metastases were found in 39% women. Of the 938 patients with IDC, 70% were Grade III and in patients where receptor status was known, 209/625 (33%) were ER positive and 245/591 (41%) were PR positive. RESULTS: The 5- and 10-year actuarial overall survival was 87% and 77% and disease-free survival was 76% and 68%, respectively. Actuarial 5-year local and locoregional control rates were 91% and 87%, respectively. Cosmesis was good or excellent in 78% women. Independent adverse prognostic factors for local recurrence were, age<40 years, axillary node metastasis, lymphovascular invasion (LVI), and adjuvant systemic therapy; for locoregional recurrence-inner quadrant tumor, axillary node metastasis, and LVI; for survival-LVI and axillary node metastasis. CONCLUSION: Compared to Caucasians, these Indian women undergoing BCT were younger, had larger, higher grade, and receptor negative tumors. Comparable local control and survival was obtained by using stringent quality assurance in the diagnostic and therapeutic protocol. BCT, a resource intense treatment is safe for selected and motivated patients undergoing treatment at centers with adequate facilities and expertise even in countries with limited resources.     

Staging and management of axillary lymph nodes in patients with local recurrence in the breast or chest wall after a previous negative sentinel node procedure

Objective

To evaluate axillary staging and management in patients with local recurrence (LR) after a previous negative sentinel lymph node biopsy (SNB).

Methods

Between 1999 and 2008, 130 patients with previous negative SNB developed a LR of breast or chest wall. After examination of clinical records, 70 patients met the inclusion criteria and remained available for analysis.

Results

Thirty-seven patients were treated with axillary lymph node dissection (ALND), followed by axillary radiotherapy in 9 cases. In 26 of these 37 patients no positive axillary lymph nodes were found. Nineteen patients received no treatment of the axilla at all. Of those, 9 were older than 70 years of age at diagnosis of LR. In 13 patients a second SNB was attempted, but was successful in only 5 cases. Eight patients underwent a complementary ALND. Overall, positive lymph nodes were detected in 13 of the 50 patients who underwent axillary staging, either by SNB or ALND. The median length of follow-up of the 70 patients following their diagnosis of LR was 24 months (range 2–81 months). During this follow-up period one patient developed an axillary recurrence. This was a patient who refused to undergo ALND but was given locoregional radiotherapy instead.

Conclusions

In the absence of guidelines for staging and management of the axilla at time of LR of breast or chest wall, many different strategies are being used. Considering the high rate of positive axillary lymph nodes in these patients, repeat surgical staging is appropriate.     

Five-node biopsy of the axilla: an alternative to axillary dissection of levels I-II in operable breast cancer.

BACKGROUND: Axillary clearance of patients with early breast cancer is accompanied by a high risk of arm morbidity. Less invasive ways to establish the axillary nodal status are therefore of interest, especially in women with low risk of nodal metastases. METHODS: Four hundred and fifteen breast cancer patients (clinical stage T(0-3) N(0-1) M(0)) were operated in the axilla with a five-node biopsy followed in the same operation by a further dissection of levels I-II of the axilla in order to evaluate the accuracy of the five-node node biopsy compared with level I-II dissection. RESULTS: In all patients the sensitivity of the five-node biopsy was 97.3% with a negative predictive value of 98.5% and a negative likelihood ratio of 0.027. Among cases detected by screening (n=204) and those clinically detected (n=197) the sensitivity of the five-node biopsy was 95.8% and 97.9% respectively, with negative predictive values of 98.7% and 98.0% and negative likelihood ratios of 0.042 and 0.021 respectively. CONCLUSION: Five-node biopsy of the axilla has good accuracy for correctly staging the axilla in both clinically and screening-detected cases. Five-node biopsy is an alternative to axillary clearance and sentinel node biopsy in patients with operable breast cancer. Copyright Harcourt Publishers Limited.     

Axillary metastasis as first symptom of occult breast cancer: a case report

Axillary lymph node metastasis from an occult breast carcinoma is a rare occurrence. We report this condition in a 59-year-old woman who presented with a swelling in the right axilla. No breast mass was clinically evident. Mammography, ultrasonography and multiple random fine-needle breast biopsies yielded no pathological findings. No extramammary primary lesions were present. Axillary sampling was performed and histological examination revealed the presence of metastatic adenocarcinoma in three of the 12 dissected lymph nodes. Estrogen receptors were positive and immunohistochemistry pointed to a breast origin. All these data were suggestive of occult breast cancer. The patient refused any further treatment but accepted clinical and radiological follow-up. Eight years later mammography revealed in the same breast a 10-mm nodule containing microcalcifications, which was not evident at physical examination. The patient underwent a lumpectomy. Intraoperative histology was positive for breast carcinoma and complete axillary clearance was performed. Histological examination revealed a lobular invasive breast carcinoma and the presence of micrometastasis in one of the 23 removed lymph nodes. The patient was given radiotherapy to the breast and axilla and tamoxifen. At present, one year after the appearance of the primary tumor, she is free of disease. Based on this case report we suggest an eclectic approach in the management of patients with axillary metastasis from occult breast cancer, depending on the clinical, pathological and biological findings.     

Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy.

BACKGROUND: The need to dissect axillary nodes in patients with early breast cancer and clinically negative axilla remains controversial. The aim of the study was to assess the role of axillary radiotherapy (RT) in reducing axillary metastases in patients with early breast cancer who did not receive axillary dissection. PATIENTS AND METHODS: From 1995 to 1998, 435 patients over 45 years old with breast cancer up to 1.2 cm and no palpable axillary nodes were randomized 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT. RESULTS: After a median follow-up of 63 months, overt axillary metastases were fewer than expected: three cases in the no axillary treatment group (1.5%) and one in the RT group (0.5%). Expected cases were 43 in the no axillary treatment group and 10 in the RT group. Rates of distant metastases and local failures were low, and 5-year disease free survival was 96.0% (95% confidence interval, 94.1%-97.9%) without significant differences between the two arms. CONCLUSIONS: This study suggests that occult axillary metastases might never become clinically overt and axillary dissection might be avoided in patients with small carcinomas and a clinically negative axilla. Axillary RT seems to protect the patients from axillary recurrence almost completely.     

Axillary surgery in breast cancer management--background, incidence and extent of nodal spread, extent of surgery and accurate axillary staging, surgical procedures

The prime objectives of axillary surgery in the management of breast cancer are 1) accurate staging, 2) treatment to cure and 3) quantitative information of metastatic lymph nodes for prognostic purposes and allocation to adjuvant protocols. It is generally agreed that axillary node status in potentially curable breast cancer is considered the single best predictor of outcome and the main determinant of allocation to adjuvant therapy. No physical examination, no imaging techniques, and no molecular biologic markers can today replace axillary surgery for staging purposes. The objectives of axillary surgery are best obtained by carrying out a complete axillary clearance. Nonetheless, less radical surgery is generally performed by carrying out a sampling procedure with a yield of about 4 nodes or a partial axillary dissection level I-II with at least 10 nodes recovered. Understaging the axilla is detrimental to outcome and, furthermore, locoregional tumor control is important for survival. Axillary surgery should therefore be conducted in accordance with high professional standards.     

The role of surgery in metastatic breast cancer

Some of the patients who present with breast cancer already have distant metastatic disease. According to recent literature, these patients may benefit from resection of the breast tumour. One explanation for the effect of this resection is that reducing the tumour load influences metastatic growth. Results of future randomised controlled trials should indicate whether surgery of the breast tumour truly improves survival. Selected patients could even benefit from metastasectomy of liver and lung metastases; survival seems to improve and these procedures seldom lead to major complications. When metastasectomy is not possible, minimally invasive techniques can be used in selected patients for the treatment of breast cancer liver metastases, radiofrequency ablation (RFA) being discussed most in the literature. Patients with locally advanced breast cancer are treated multidisciplinarily and with curative intent. Part of the treatment is surgery to reduce tumour load. Regarding treatment of the axilla, in a clinically negative axilla sentinel node biopsy is advised before neoadjuvant treatment; an axillary lymph node dissection is not warranted. In local recurrence, surgery is the primary treatment. Axillary staging can be done in patients with a previous negative sentinel node biopsy. Regional recurrence after breast-conserving surgery or mastectomy is treated with surgery followed by radiotherapy.     

Can axillary and supraclavicular radiotherapy be avoided after breast-conserving surgery and axillary dissection in women with multiple involved axillary nodes? Experience at the European Institute of Oncology

AIMS AND BACKGROUND: Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular nodes if 4 or more axillary nodes are involved, the current practice at our Institute is not to irradiate the axilla but to perform complete axillary dissection in which all 3 Berg levels are removed. We performed a retrospective analysis of patients with 4 or more axillary nodes involved and sufficient follow-up to provide indications as to whether our current treatment is adequate. METHODS: We retrospectively analyzed 287 T1-T3 patients with a median follow-up of 5 years and 4 or more involved nodes treated by quadrantectomy and breast RT but no axillary RT; supraclavicular RT was given only when prognostic factors were unfavorable. RESULTS: A total of 170 (59.2%) patients did not receive supraclavicular RT, while 117 (40.8%) patients received supraclavicular irradiation. No patient received axillary RT. After a median follow-up of 5 years (range, 4-105 months), 4.7% had died and 13.5% had developed distant metastases in the no supraclavicular RT group, compared to 12.0% dead (P = 0.028 log rank) and 24.8% (P = 0.201 log rank) in the supraclavicular RT group. No patients with supraclavicular RT developed supraclavicular metastases compared to 4 in the no supraclavicular RT group. There were no axillary recurrences. CONCLUSIONS: Complete axillary dissection appears adequate treatment in patients with 4 or more involved nodes. The low breast recurrence rate also suggests that breast conservation is adequate treatment in such patients. Supraclavicular RT appears to reduce the number of supraclavicular metastases but confers no survival advantage. Although a small number of cases were examined in this retrospective single-center series, all received highly uniform treatment.     

Sentinel node micrometastases in breast cancer: clinical outcome

Aim: The sentinel lymph node biopsy has steadily replaced axillary lymph node dissection for staging clinically node‐negative breast cancer. This study assesses surgical and adjuvant practice in relation to micrometastases and isolated tumor cells found on biopsy in a single surgeon cohort. Methods: Clinicopathological characteristics were collated from 700 breast cancer patients undergoing sentinel lymph node biopsies between 1999 and 2007. The status and details of the node biopsies, continuing treatment and adverse outcomes were reported. Patient details at the time of diagnosis were entered into Adjuvant! online to look at likely prognosis. For both isolated tumor cells and micrometastases, data input was conducted twice, once as node‐negative and again as node‐positive, thus providing two predicted benefit data series. Results: A total of 665 women were eligible for inclusion, 67 with micrometastases and 20 with isolated tumor cells. Overall 33 patients developed recurrence with nine breast‐cancer related deaths. Women with isolated tumor cells or micrometastases were more likely to receive adjuvant radiotherapy to the axilla compared with women with node‐negative disease. Compared to those with isolated tumor cells, a higher number of women with micrometastases received systemic chemotherapy despite similar predicted benefits. Individual comparisons showed significantly higher rates of recurrence in women with isolated tumor cells than in node‐negative disease (P < 0.0001). Conclusion: The biological behavior of early breast cancer with isolated tumor cells on sentinel node biopsy is similar to both micrometastases and macrometastases, i.e. they behave in a node‐positive fashion. This is an early indication that these patients should be treated with more aggressive adjuvant therapy.     

Interpectoral approach to dissection of the axillary apex: an elegant and effective approach

BACKGROUND: Axillary dissection is the gold standard for treatment of the axilla. It provides important prognostic information, accurately stages the axilla, and has the lowest recurrence rate among all modalities. In today's age of conservation surgery, the axilla is often addressed through a cosmetically acceptable small incision with limited access, thereby making clearance of the level III nodes difficult. METHODS: We describe a method of apical lymph node dissection through the interpectoral plane, which effectively clears the apex despite the constraints of limited exposure. RESULTS: This method has been used in nearly 5,000 axillary dissections performed at our institute, with excellent results. It preserves the innervation of the pectoral muscles and affords access to the interpectoral nodes. CONCLUSIONS: Our method has a short learning curve, provides good exposure of a difficult area and consistently provides a good yield of nodes.     

Presentation of axillary lymphadenopathy without detectable breast primary (T0 N1b breast cancer): experience at Institut Curie

Between 1960 and 1985, 31 patients presented to Institut Curie with isolated axillary lymphadenopathy, of probable metastatic origin from the breast, but without clinical or radiological evidence of a breast tumor and no other primary tumor. The mean age was 54.6 years (range 39-79 years). Histological diagnosis was obtained by axillary surgery (22 cases), drill biopsy (6 cases), and cytology (3 cases). All slides were reviewed for the present study. Treatment consisted of axillary surgery followed by radiotherapy in 22 patients, radiotherapy followed by axillary surgery in 6 patients, radiotherapy followed by modified radical mastectomy in one patient, and radiotherapy alone in 2 patients. Systemic adjuvant treatment was given to 11/31 patients. The median follow-up was 9 years (range 2-26 years). Eight recurrences have appeared. Four patients recurred in the breast only (mean time to relapse: 112 months, range 63-162 months). The four other patients recurred both in breast and/or axilla (mean time to relapse: 23 months, range 7-46 months). Nine patients have developed distant metastases, of whom three also had locoregional recurrence. Among the 11 patients who had had systemic treatment, 5/11 had recurrence or metastases. The overall 5 and 10 year actuarial survival rates were 76 and 71%, respectively. The metastasis-free 5 and 10 year actuarial survival rates were 73 and 71%, respectively. Axillary metastases without clinical or radiological evidence of a primary breast tumor represents a discrete clinical entity, the prognosis of which appears to be better than that of clinical invasive breast cancer with associated lymph node involvement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of the axilla in conservatively treated breast cancer: 592 patients treated at Institut Gustave-Roussy

Between June 1970 and April 1982, 592 patients with unilateral T1 and small T2 breast cancers were managed conservatively at the Institut Gustave-Roussy. The treatment policy for the axilla was to perform a lower axillary dissection and to proceed to axillary clearance ( +/- radiotherapy) in patients with axillary invasion by tumor (N+). Some N+ patients had only lower axillary dissection and radiotherapy. Five hundred fifty-eight patients underwent axillary surgery which was a lower axillary dissection in 374 patients (67%) and axillary clearance in 184 patients (33%). There was axillary invasion in 198 cases (36%). Only five patients relapsed in the axilla and the probability of axillary relapse at 5 years was 1.2%. There were no axillary relapses in N+ patients who had had an axillary clearance whether irradiated or not. The incidence of upper limb complications was significantly greater in patients undergoing axillary surgery and radiotherapy compared with axillary surgery alone (p less than 0.0001). It is concluded that a lower axillary dissection accurately identifies N-patients and an axillary clearance in N+ patients ensures good local control and avoids the morbidity associated with axillary irradiation.     

Complete axillary conversion after neoadjuvant chemotherapy in locally advanced breast cancer: a step towards conserving axilla?

OBJECTIVES: This study was designed to assess the clinical, sonographic and histopathological response of axillary lymph node metastasis to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIAL AND METHODS: Forty patients with locally advanced breast cancer (LABC) with clinically palpable or sonographically detectable axillary nodes were studied. FNAC of the primary tumor and axillary nodes was done and patients were started on neoadjuvant chemotherapy. Axillary nodes were assessed clinically and sonographically for response after 3 cycles of chemotherapy. All patients underwent total mastectomy with axillary clearance and the lymph nodes in the specimen were examined for metastasis. RESULTS: 47% patients had complete clinical nodal response, while 19% showed complete sonographic response. Complete pathological nodal response was documented in 22% of patients. Ultrasonography was found to be more sensitive than clinical examination in assessing complete nodal response. 10% of the patients had complete pathological response of both primary tumor and axillary nodes. There was significant correlation between pathological response of primary tumor and lymph nodes (P=0.004). Patients with complete sonographic or clinical response were found to have no or minimal residual disease in axilla and hence axillary dissection may be avoided in them.