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This article was taken from Medscape and was written by
Nicole MA Krekel; Barbara M Zonderhuis; Hermien WH Schreurs; Alexander MF Lopes Cardozo; Herman Rijna; Henk van der Veen; Sandra Muller; Pieter Poortman; Louise de Widt; Wilfred K de Roos; Anne Marie Bosch; Annette HM Taets van Amerongen; Elisabeth Bergers; Mecheline HM van der Linden; Elly SM de Lange de Klerk; Henri AH Winters; Sybren Meijer; Petrousjka MP van den Tol
Background: Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life.
Methods/design: In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described.
Conclusion: The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life.
Discussion and Conclusion
The goals of breast-conserving surgery are to obtain adequate margins and good cosmetic results. Both goals are poorly defined, and there is no universal acceptable standard. According to Dutch national guidelines, a negative margin is defined as a margin of ≥ 1 mm of normal tissue intervening between the tumour and the edge of the specimen. Resections are described as focally involved when cancer cells invade the resection margin in a maximum of two microscopic slides or when margins include < 1 mm of normal tissue. The margins are described as involved or positive when microscopic cancer cells are situated on the inked resection border. It has been well-established that the status of the margin affects the local recurrence rate. Therefore, re-excision is indicated for involved margins. Vrieling et al. showed that patients with focally involved margins have lower rates of recurrence when treated with a higher radiation boost dose, equal to patients with adequate margins. Therefore, a higher boost dose is given to patients with focally involved margins without further surgery. This has been confirmed by national guidelines.[15–19]
To analyse cosmetic outcomes, frequently used subjective methods are patient self-evaluation and panel evaluation. Patient self-evaluation is a valuable method as the patient's opinion is of great importance; however, patients tend to report consistently better scores than professionals. Panel-evaluation, consisting of a panel of six professionals and non-professionals, has proven to be the most reliable subjective method. The panel evaluates 4-point view pictures of the breasts.[8,13] Breast Retraction Assessment (BRA) is a well-validated and frequently used objective method to evaluate breast asymmetry. The BRA is reliable and minimally time-consuming; however, it is only correlated moderately for tumours located in the lower quadrant, and skin changes (e.g. disturbing scars or telangiectasias) are not taken into account. In the framework of the EORTC trial, Vrieling et al. compared these different methods of cosmetic outcome assessment. The BRA is recommended for comparing the cosmetic outcomes between two different approaches to BCT and for analysing cosmetic changes over time. The panel evaluation gives the best measure of the overall cosmetic result. Therefore, in order to assess cosmetic outcomes, the most appropriate method is to combine the panel evaluation and the BRA into an overall score. Patient self-evaluation is necessary with regard to quality of life.[30,31]
The excision of nonpalpable breast cancer can be performed with guidance from several tools. The wire-localisation (WL) is still the gold standard. The WL procedure is technically demanding and depends on both the wire placement by the radiologist and on the experience and three-dimensional orientation of the surgeon. The insertion of the wire can be uncomfortable for the patient; Furthermore, there is a risk of wire migration between the time of insertion and the beginning of the surgery. Other less frequently used techniques are emerging, including the use of radioactive seed implants, an electrosurgical loop device and Radio-guided Occult Lesion Localisation (ROLL), which uses a radioactive pharmaceutical that is injected into the tumour pre-operatively. A gamma probe is used to guide the surgical resection. A drawback is that these guidance tools are invasive. Currently, these techniques are being validated.[32–34] Intra-operative ultrasonography (US) was introduced in 1988 as an easily available and patient-comfortable method of excising a tumour under direct vision. Using intra-operative US, surgeons can localise and guide the excision of non-palpable lesions, without the need for additional interventions before surgery. After specimen removal, the US is valuable to confirm excision and check margin clearance before wound closure. However, a possible restriction is the arrangement of a radiologist's presence in the operating theatre. In our multicentre study wire-localisation (WL), ROLL and USS were retrospectively compared. USS was clearly the most effective method for the excision of nonpalpable tumours.[27] Moreover, a number of studies such as Rahusen et al. and Snider et al. have clearly demonstrated that intra-operative US guidance has considerable advantages over wire-guided excision, including reduced pre-operative stress and discomfort for patients and decreased operating room time. Most importantly, intra-operative US guidance resulted in improved resection margins and smaller excision volumes.
High-frequency US shows most lesions, and in general, all palpable breast lesions are visible with ultrasonography (US). Therefore, intra-operative US is applicable in the majority of women with a palpable breast cancer.[21–26,28,33]
Intra-operative ultrasonography will contribute to improved cosmetic outcomes by:
1. Smaller volumes of resected breast tissue
2. Improvement of margin status
- avoiding a higher boost dose for focally involved margins
-avoiding re-excision or even mastectomy for involved margins
Approximately 9000 out of 13000 breast cancer patients are diagnosed with a palpable breast cancer in the Netherlands each year, and around 5000 patients undergo breast-conserving surgery for a palpable breast cancer. An improvement of cosmetic outcomes in an estimated n = 1115 (22.3%) of all patients treated with breast-conserving surgery can be achieved by USS. Also, an estimated n = 875 (17.5%) less operations will be necessary after treatment by US-guided surgery (A re-operation costs about € 7 000, -, so eventually € 6 125 000, - might be saved by this method each year).
In conclusion, this randomised controlled trial aims to demonstrate the superiority of USS versus PGS for the treatment of patients with palpable breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life.
This post was edited by Cynthia at October 18, 2011 10:06:41 AM WATime"
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