D. Ravichandran

Ultrasound and fine needle aspiration cytology of the axilla in the pre-operative identification of axillary nodal involvement in breast cancer

AIMS Pre-operative diagnosis of axillary nodal involvement in breast cancer allows one-stage axillary surgery. We evaluated the efficacy of axillary ultrasound (US) with US guided fine needle aspiration cytology (FNAC) in the diagnosis of axillary nodal involvement. METHODS Over a 13-month period, we performed US of 369 axillae in patients with screen-detected (n = 278) and symptomatic (n = 91) invasive carcinoma of the breast, at the same time as US of the primary tumour. If abnormal lymph nodes were demonstrated, a single US guided FNAC of the most abnormal node was performed. US and FNAC results were compared with the final histology of the surgically excised lymph nodes. RESULTS Among the 369 axillae studied, 102 had nodal macrometastases and 38 (37%) were identified by US guided FNAC. The rate was 33% in screen-detected and 44% in symptomatic patients. Sensitivity increased with increasing numbers of positive axillary nodes, and the more abnormal the appearances of the nodes on US. CONCLUSION US with FNAC of the most abnormal node allows pre-operative detection of a third of node positive axillae in screen-detected and over 40% of those with symptomatic breast cancer, allowing one-stage axillary surgery avoiding the sentinel node biopsy step in these patients.

A pilot study of dual-isotope lymphoscintigraphy for breast sentinel node biopsy comparing intradermal and intraparenchymal injection

AIMS Identification of sentinel lymph nodes (SLN) may depend on the tissue plane of tracer injection. To explore this, we developed a dual-isotope technique to compare the lymphatic drainage basins accessed by intradermal and parenchymal injections. METHODS Fifteen breast cancer patients had simultaneous parenchymal and intradermal injections of (99m)Tc-labelled human immunoglobulin G (HIG) and (111)In-HIG, respectively, 2-4h before axillary lymph node clearance surgery. All 228 freshly dissected nodes were assayed by well counting and examined for metastatic disease by haematoxylin/eosin staining and immuno-histochemistry. RESULTS Total nodal uptake following intradermal injection was 10 times more than after parenchymal injection. Tracer uptake within the first three draining nodes divided patients into three groups; four (group 1) had identical 1st, 2nd and 3rd echelon nodes, six (group 2) had identical 1st and 2nd echelon nodes and five (group 3) had different 1st echelon nodes. With respect to the first, second and third groups, there was close, moderate and poor correlation (Pearson), respectively, between individual nodal counts accumulated from the two injection sites. Of eight patients with nodal disease, the SLN identified by intradermal and parenchymal injections contained disease in seven and four patients, respectively. CONCLUSIONS Comparison of nodal tracer distributions from the two injection planes allows a functional model to be developed with two possible routes of drainage from the parenchymal plane, one joining the tract from the areolar plexus and the other passing independently to the axilla which builds upon Sappeys original anatomical model. This may explain the variable uptake, discordance and false negative SLN identification.

Functional variation in lymph node arrangements within the axilla

The aim of the project was to identify how lymphatic pathways are functionally arranged within the axilla (i.e., single linear chains, branching chains, and networks). We used ex vivo dual isotope radioassay of individual nodes resected at axillary lymphatic clearance surgery in breast cancer patients given simultaneous intradermal breast and intradermal hand injections (n = 15) or simultaneous intradermal breast and parenchymal breast injections (n = 15) of differentially labelled human immunoglobulin (Tc-99m-HIG and In-111-HIG). Nodes were ranked according to isotope content and activity-rank profiles constructed for each of the two injection sites. The majority of profiles following intradermal breast injection (17/30) were mono-exponential, consistent with a simple linear chain of nodes, with each node extracting a constant fraction of incoming HIG. In 15/17 of these, the accompanying profile from the alternative injection site was also mono-exponential and, in 11/15, essentially parallel. The profile appeared biphasic in 12/30 intradermal breast injections and of these 9/12 were accompanied by a biphasic profile (7/9 parallel) from the alternative injection site. In one patient, both profiles were polyphasic and parallel. Considering the respective shapes of paired profiles and whether the two injection sites shared the same first echelon nodes, functional lymph node arrangements are proposed. The commonest is a single linear chain, then a chain branching into two linear chains, and, least common, a network.

Adjuvant therapy decisions in breast cancer: comparison of a multi disciplinary team's decisions with the recommendations of web-based computer programme “Adjuvant Online”.

Abstract #2117 Introduction: Adjuvant therapy decisions in breast cancer impact on survival, recurrence and quality of life. We compared the hormonal and chemotherapy recommendations of a multi-disciplinary team (MDT) with the “best treatment” recommended by an evidence-based online computer programme “Adjuvant Online” (AO).
 Materials and Methods: We prospectively monitored a breast cancer MDT for a period of one year. Among 218 breast cancer patients discussed, patients who had DCIS, neoadjuvant therapy, primary hormonal therapy, multifocal disease and micrometastases only in the axillary lymph nodes and recurrent disease were excluded leaving 122 suitable for input into AO. The MDT recommendation and actual treatment received were recorded. Ten-year cancer-related death and relapse rates were calculated using AO and estimates of proportional risk reduction with MDT recommended therapy and AO “best treatment” were made.
 Results: Median age was 61 years (range 28-86). MDT recommended endocrine therapy (ET) to all patients with ER/PR positive cancers (n=103). Among 30 women aged 55 years or less with ER/PR positive cancers, 25 had tamoxifen, 4 had an aromatase inhibitor (AI) and one switched from tamoxifen to an AI. AO suggested AI or tamoxifen-AI switch as the best treatment for post-menopausal women. Among 73 women aged over 55 years with ER/PR positive cancers, 46% (n=34) received tamoxifen as per local cancer-network guidelines, which recommended tamoxifen for low-risk (T1 N0 M0) post-menopausal breast cancer. Others received an AI (n=38) except one patient who declined ET. There were 54 patients with >10% risk of cancer-related death in 10 years. Among these 36 were offered and 29 received chemotherapy. Chemotherapy was not offered to 17 patients due to age and/or comorbidity. Only 1 suitable patient with >10% risk was not offered chemotherapy by the MDT. Among those who had chemotherapy, only 31% had 3rd generation chemotherapy as recommended by AO, the main reason being national guidelines in the United Kingdom limiting the use of this regimen.
 Discussion: There are differences between the adjuvant therapy decisions by the MDT and the “best treatment” recommended by Adjuvant Online. This study shows that in the majority of these cases the differences are due to either local or national guidelines that are in force in the United Kingdom. Cancer MDTs in the UK National Health Service are expected to adhere to these guidelines. However, calculation of the risk of death and recurrence rates using AO may be useful to facilitate decision making of the MDT by giving quantitative prognostic estimates and this could be a useful adjunct to help patients make informed decisions. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2117.

Adjuvant! Online does not significantly influence adjuvant chemotherapy decisions of a breast cancer multidisciplinary team (MDT): a prospective study

One of the most difficult tasks of a breast cancer multidisciplinary team (MDT) is to decide on the need for adjuvant chemotherapy (CT) in patients with invasive breast carcinoma. While the need for adjuvant endocrine therapy is largely determined by a single factor (hormone receptor positivity), the need for adjuvant CT is determined by multiple factors such as patient age, tumour size, grade, node positivity and hormone receptor and human epidermal receptor growth factor-2 receptor status. The UK National Institute for Health and Clinical Excellence (NICE) recommends using Adjuvant! Online, an online computer programme that allows quantitative estimates of the effect of adjuvant CT on the 10year risk of death and relapse in the MDT decision-making process [1]. The majority of breast oncologists use Adjuvant! Online in their clinical practise [2], however we previously reported in a retrospective study [3] that the use of Adjuvant! Online in an MDT did not change the management in the majority of cases. In this audit we prospectively studied the impact of Adjuvant! Online-derived numerical estimates of CT benefit on the MDT decision-making process. We studied 109 early breast cancer patients discussed in 41 MDT meetings over 12 months. All had unilateral, unicentric, invasive adenocarcinoma and had undergone breast surgery and axillary node staging. Patients who had neoadjuvant therapy or

Follow-up of benign screen-detected breast lesions with suspicious preoperative needle biopsies

AIM To study the outcome of patients with screen-detected breast lesions in whom preoperative core biopsy (CB), or fine needle aspiration cytology (FNAC), or both were suspicious of malignancy or malignant, but the final histology of the excised lesion was benign. MATERIALS AND METHODS Thirty-nine patients who fulfilled the above criteria were identified from a prospectively entered database of 192,153 breast screening examinations at the Bedfordshire and Hertfordshire Breast Screening Unit. Thirty-four patients had suspicious or malignant preoperative FNAC and/or CB, and five had FNAC only. Follow-up was mainly by mammograms. Outcome data were collected from hospital case notes and radiology reports. RESULTS The median follow-up period was 3 years following excision biopsy. One patient whose excision biopsy histology was atypical ductal hyperplasia developed a mammographically occult carcinoma in the same breast after 24 months. There were no other cancers reported during this time. CONCLUSION The problem of suspicious preoperative needle biopsies with benign excision biopsy is uncommon in the breast screening population. These patients are not at an increased risk of being diagnosed with a carcinoma in the subsequent 3 years and may be discharged back to standard breast screening.

Ductal Carcinoma In Situ of the Breast: Is Clinical Follow-up Necessary after Treatment?

Sird There is an ongoing debate and discussion regarding the optimum follow-up strategy after breast cancer therapy and the value of clinical follow-up has been questioned. Ductal carcinoma in situ (DCIS) constitutes about 20% of screen-detected breast cancers. It is treated with breastconserving surgery (BCS) with or without radiotherapy, or mastectomy, and has an excellent prognosis. DCIS patients are, however, not distinguished as a separate category from those with invasive cancers with regards to follow-up, and follow-up practices differ widely [1].We have been following up patients treated for DCIS onlywithmammogramswith no scheduled clinical follow-up since 2006 and reviewed 101 patients treated between 2005 and 2008 to study the adequacy of such follow-up. Patients still had access to a breast clinic via the breast care nurses or general practitioners. Seventy-nine patientswere screen-detected. Themedian age was59years (35e84). Sixty-nine underwent BCS andof these 24 required re-excision of radial margins, final radial margins being >2 mm in all patients. Others (n 1⁄4 32) had a mastectomy (13 with reconstruction of the breast). Forty-one patients received radiotherapy and five with micro-invasion received endocrine therapy. Mammograms were carried out yearly after BCS, and 1, 3 and 5 years after a mastectomy. Patients were generally discharged after 5 years. Follow-up datawere available in 96 patients. Themedian follow-up was 57 months (28e81). Forty-nine patients had mammograms only and no clinic visits. Others had one or more clinic visits. Therewere 91 clinic visits in total, thus the number of visits on averagewas less than one per patient for the 57monthperiod. Someof these visitsweremade in error by the hospital and others by patients/general practitioners. Therewere two ipsilateral recurrences, bothDCIS, and three new cancers on the contralateral side; one DCIS and two invasive carcinomas. These were not palpable and were diagnosed on mammograms, except for one patient with contralateral invasive carcinoma who felt a thickening in the breast andwas referred by the general practitioner.No recurrences or contralateral cancers were detected during clinic visits. Most breast relapses are now detected by patients or mammography [2]. Abouthalf the recurrencesafterprevious DCIS are again DCIS, which are usually impalpable [3] and often detected by mammography [4,5]. There is a wide variation in the follow-upofDCISpatients in theUK; a survey of 66UKbreast units revealed 12e14 different frequencies of clinical follow-upwith a total follow-upperiod ranging from zero to indefinite, and 10e11 different frequencies for mammograms with a follow-up period from 2 years to indefinite [1].We conclude that following uppatientswhohad treatment for DCIS with mammograms only would result in cost savings without compromising the outcome.

Axillary Lymph Node Drainage Pathways from Intradermal and Intraparenchymal Breast Planes

BACKGROUND To compare functional anatomy of breast peri-areolar and peri-tumoral lymphatic drainage basins. METHODS Fifteen breast cancer patients received simultaneous peri-areolar (intradermal) and peri-tumoral (intraparenchymal) injections of human polyclonal immunoglobulin (HIG) labeled with (99m)Tc and (111)In 2 to 4 h before axillary lymph node clearance surgery. Resected nodes (range 5-20; median 16) were individually counted for (99m)Tc and (111)In in a well-counter and ranked according to activity content (echelon). Activity in distal nodes was negligible so extraction efficiency (E) of HIG in the first echelon node was calculated as counts divided by total counts in the chain. RESULTS Five- to 10-fold more activity was recovered after intradermal injection. The injection planes identified the same first echelon node in 10 patients (group 1) but different in five (group 2). In group 1, intradermal E correlated with intra-parenchymal E (r = 0.82; P < 0.01). E of intradermal first echelon nodes in group 2 was 51 (SD 13)%, similar to intradermal E in group 1 (58 [23]%). E of intraparenchymal first echelon nodes in group 2, however, was 28 (6)%, lower than intraparenchymal E in group 1 (54 [20]%; P < 0.02). CONCLUSIONS Lymph nodes extract approximately 50% of HIG. Extracted HIG does not cascade to distal nodes, validating HIG for sentinel node lymphoscintigraphy. HIG injected intradermally at the areola drains via a single route to the axilla. In two-thirds of patients, peri-tumoral HIG follows a similar route, but in one-third of patients drainage from the parenchymal plane is more complex, with more than one route to the axilla.

Measurement of lymph node function from the extraction of immunoglobulin in lymph

Abstract Background. We aimed to measure the extraction fraction of human immunoglobulin G (HIG) by the 1st echelon lymph node (sentinel node) following intradermal injection in patients with breast cancer undergoing axillary lymph node dissection (ALND) and examine its association with node size and presence and extent of nodal metastatic disease. Materials and methods. HIG labelled with either In-111 (n = 21) or Tc-99m (n = 9) was injected intradermally at the areolar. ALND was performed 2–4 h later. All lymph nodes were isolated and individually counted in a well-counter. The counts in the ‘hottest’ (1st echelon) node were expressed as a fraction of total counts in all the resected nodes. Since counts in the least hot nodes barely exceeded background, this fraction represents extraction fraction for the 1st echelon node. Presence of disease was noted in each 1st echelon node and the extent quantified as percentage replacement with disease. Results. Median extraction fraction in 1st echelon nodes with no or low (<1%) disease burden (n = 21) was 68 (range 23–93)%, significantly higher (p<0.05) than in diseased 1st echelon nodes (n = 9), in which it was 44 (21–66)%. There was, however, no association between extraction fraction in diseased nodes and disease extent. In nodes with no/low disease, extraction fraction was similar for the two radiolabels. There was no association between extraction fraction and node size. Conclusion. Nodal extraction fraction of HIG is a novel physiological measurement. It is reduced as a result of metastatic invasion. In the absence of disease, it shows no correlation with node size.

Discolouration of breast skin following breast conservation therapy for breast cancer: a cautionary tale of two patients

Recurrence of malignancy in the treated breast following breast conservation therapy (BCT) occurs in a minority of patients, but is a significant clinical problem. This is often detected on follow-up mammography (1). Skin discolouration as the initial presentation of recurrent malignancy is rare. We report two such cases where one patient had recurrence of breast cancer and the other had radiation-induced angiosarcoma of the breast.