Breast Surgery: Margin Assessment and Complications

Maiju Lepomäki

Research output: Book/ReportDoctoral thesisCollection of Articles

Abstract

The surgical oncology of breast cancer aims to remove the entire tumor with sufficient surgical margins. Inadequate margins increase the risk of a local recurrence and impair the overall survival of patients. Thus, inadequate margins often necessitate a reoperation. The margin status is determined postoperatively by a pathologist during the gross and microscopic examination of the surgical specimen. However, gross examination is not always straightforward, and the optimal margin width for ductal carcinoma in situ (DCIS) diagnosed alongside invasive carcinoma remains controversial.Currently, approximately one in five patients undergo a reoperation after breast- conserving surgery (BCS), but the reoperation rates do not equal positive margin rates and there is considerable variation in reoperation practices. In this doctoral thesis, we provide a detailed assessment of histopathology reports to better understand the factors that lead to a reoperation (study III).

Reduction mammoplasty is an elective operation, whereas breast cancer surgery is performed on a vital indication. However, the postoperative complication profiles of reduction mammoplasty, BCS, and mastectomy reflect one another. The examination of postoperative complications after reduction mammoplasty also provides data on the recognition of high-risk patients in surgical oncology. Herein, we investigate a series of reduction mammoplasties to assess the risk factors for complications after reduction mammoplasty (study I).

A tool for intraoperative breast cancer identification could reduce reoperations due to margin positivity. Similarly, tissue imaging before a pathological gross examination could enable focused sampling of breast specimens without compromising diagnostic accuracy. In recent years, such methods have been extensively studied, but none have been adopted into routine practice. Differential mobility spectrometry (DMS) enables the analysis of complex gas mixtures. DMS can offer a robust and cost-efficient means of breast cancer identification from evaporated tissues. We present two DMS-based systems for 1) intraoperative margin assessment (study II) and 2) tissue imaging (study IV).

In study I, we analyzed the clinical data of patients who underwent reduction mammoplasty at Tampere University Hospital (Tays) between 2007 and 2010 (n =453). Complications treated on an outpatient basis were classified as minor and those demanding readmission or a reoperation as major. In study III, we analyzed the histopathological data of breast cancer patients (n = 4,489) operated on at Turku University Hospital (Tyks) between 2000 and 2018. Margin positivity was defined as ink on tumor for invasive carcinoma. For DCIS, we applied 2 mm anterior and side margin thresholds and ink on tumor in the posterior margin.

We analyzed a series of porcine tissues with laser-based DMS in study IV. We examined DMS in 1) matrix-wise tissue identification and 2) the classification of an independent validation set. Next, we studied breast cancer identification with DMS in studies II and IV. The carcinoma samples were of 1) a palpable tumor and 2) tumor size exceeding 21 mm (≥ cT2). In study II, we collected malignant and benign punch biopsies (4 mm) from twenty-one breast cancer patients. The samples were analyzed with the Automated Tissue Analysis System (ATAS), which utilized a diathermy blade for tissue evaporation. In study IV, we analyzed cross-sections of three breast carcinomas with the Automated Tissue Laser Analysis System for imaging approaches (iATLAS).

After reduction mammoplasty, the incidence of minor and major complications was 41% and 9%, respectively. Patients with minor complications had a significantly higher mean BMI (30 kg/m2) than patients who recovered without complications (28 kg/m2; p < 0.001). Patients with a BMI higher than 27 kg/m2 had a 2,6-fold greater risk of minor complications (p < 0.001). An increase of one unit in BMI increased the probability of minor complications by 14% (p < 0.001). After breast cancer, the incidence of positive side margins was higher in BCS (20%) compared to mastectomy (5%; p < 0.001). Of these patients, a respective 68% and 14% were reoperated on (p < 0.001). Young patients underwent a reoperation significantly more often (68%−74%) than those aged more than 80 years (42%; p = 0.013). DCIS located close (≤ 1 mm) to the side margin led to a reoperation in 70% of the cases, whereas those with a wider (1.1–2 mm) margin underwent a reoperation in 43% of the cases (p = 0.002). The reoperation rates were 55% for invasive carcinoma with a close DCIS margin, 66% for a close intraductal component (EIC) margin, and 83% for close pure DCIS margin (p < 0.001).

We achieved a classification accuracy of 86% for porcine skeletal muscle (n = 1,030), adipose tissue (n = 1,329), normal breast tissue (n = 258), bone (n = 680), and liver (n = 264) with DMS data. In the independent validation set analysis, we achieved a classification accuracy of 82% with the previously constructed classification model. With ATAS, the classification accuracy of breast cancer (n = 106) and benign breast tissue (n = 198) was 87%, with a sensitivity of 80% and specificity of 90%. With iATLAS, we reached a classification accuracy of 94%, specificity of 94%, and sensitivity of 93% for the macroscopically annotated data from three breast cancer specimens. The microscopic annotation was applicable to two specimens. For the first specimen, the classification accuracy was 84%, specificity 88%, and sensitivity 77%. For the second specimen, the classification accuracy was 72%, specificity 88%, and sensitivity 24%.

A higher BMI was strongly associated with an increased risk of minor complications after reduction mammoplasty. It is important to inform obese patients about the increased risk and to encourage them to lose weight before surgery. Individual assessment as opposed to rigid adherence to guidelines was applied in the decision on whether to reoperate after side margin positivity in surgical oncology. Operation type, DCIS type and the component’s distance from the side margin, as well as the patient’s age guided the decision on whether to reoperate. DMS analysis of evaporated tissues is suitable for tissue identification. In the future, DMS analysis could be efficient in intraoperative margin assessment and tissue imaging before traditional microscopy.
Original languageEnglish
Place of PublicationTampere
ISBN (Electronic)978-952-03-2849-8
Publication statusPublished - 2023
Publication typeG5 Doctoral dissertation (articles)

Publication series

NameTampere University Dissertations - Tampereen yliopiston väitöskirjat
Volume779
ISSN (Print)2489-9860
ISSN (Electronic)2490-0028

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