In 2020, breast cancer was the most diagnosed female cancer, with an estimated 2.3 million new cases (11.7%) globally. It is the fifth leading cause of cancer deaths, accounting for 6.9% of cancer deaths worldwide (1). Since 1988–1995, mortality from breast cancer has been declining sharply in most high-income countries (2). The inception of mammographic screening programs has led to increasing diagnosis of small breast cancers, many of which have favorable biological characteristics (3, 4). Some of these tumors have excellent long-term outcomes, with 10-year breast cancer specific survival approaching 100% (5). It is likely that such tumors may never become symptomatic within a patient’s lifetime due to their indolent nature and may thus represent overdiagnosis. There has been much debate around the extent of overdiagnosis within mammographic screening programs. In the UK, an Independent Panel Review of the UK NHS Breast Screening Program concluded that, for every breast cancer death prevented by screening, around three cancers were overdiagnosed and consequently overtreated (6). However, despite improvements in the understanding of tumor biology, there remains no way of identifying those small (T1a and T1b) tumors with broadly favorable characteristics (e.g., hormone receptor positive [HR+] and HER2−) that are likely to progress or to become life threatening. These patients are all generally treated the same manner, usually with breast-conserving surgery, adjuvant radiotherapy, and endocrine therapy. These treatment modalities have associated physical and psychological morbidities for patients and costs for healthcare providers (7–9). Thus, there is increasing interest in the de-escalation of loco-regional therapies for small screen-detected tumors.

Numerous image-guided ablative techniques have been described for the minimally invasive management of small tumors (10). By their nature, however, majority of these techniques do not provide tumor tissue for histopathological assessment and often require specialized equipment and expertise, which is not readily available. However, vacuum-assisted excision (VAE) is a commonly used technique for both diagnostic and therapeutic purposes and can be carried out under local anesthesia and image guidance. VAE is currently used to manage benign lesions (11) and lesions of uncertain malignant potential (B3 lesions), where the aim is to take 4 g of tissue, which would remove the lesion if small (≤ 15 mm in size) but otherwise allow representative sampling without complete resection (CR) if > 15 mm in size (12–14). More recently, there has been interest in the application of VAE for the percutaneous resection and treatment of small breast cancers to potentially reduce morbidity and surgical overtreatment of screen-detected cancers (15).

This retrospective series aimed to evaluate the role of vacuum-assisted procedures in the resection of breast cancers and support selection criteria for future prospective trials.

One thousand sixty-one diagnostic VAB procedures were reviewed. One hundred thirty-three breast cancers were identified. Seventeen cases were excluded due to lack of pathological data following subsequent surgical excision. One hundred sixteen lesions with paired VAB and surgical pathology data were evaluated ( Figure 1 ). Factors predictive of PRP were analyzed. In total, five of 116 (4.3%) cases had multicentric or bilateral breast cancers, three had VAB only of one lesion, and one had VAB from two different multicentric nodules. All cancers were reported separately in the data.

VAB is a convenient outpatient percutaneous procedures carried out under local anesthesia, which are well tolerated. They can be performed with vacuum biopsy devices, which are used globally for diagnostic purposes. This retrospective series of unselected cases submitted to diagnostic VAB showed that 25% of tumors were completely resected, with a further 15.5% of cases having MRD only. However, a further 55.2% of cases had gross residual disease following VAB, with 4.3% showing an upgrade from DCIS to invasive disease at surgery. This data suggests that with careful selection of patients likely to have very small low risk disease, or indolent disease unlikely to progress, it may be possible to completely resect breast cancer with percutaneous minimally invasive techniques.

In this series, in the group of PRP, only 23% of cases were ordinary VAB and 76% were EVAB. In the other group of tumors NPR, 58% of cases were submitted to ordinary VAB and only 42% to EVAB, showing that for potential CR purpose a EVAB procedure should be recommended. Most of the cases with CR were tumors smaller than 10 mm (96.4%), of low/intermediate nuclear grade (93.1%), IC (72.4%), presenting with a mass lesion either with or without associated mammographic calcifications (86.2%). In addition, in the PRP group 97.8% of tumors were smaller than 10 mm and 87.2% of tumors were nuclear grade 1 or 2. For invasive breast cancers, the data shows that it is possible to complete resect percutaneously invasive ductal (19 of 21, 90.5%) and invasive lobular (2 of 21, 9.5%) carcinomas of all immunohistochemical subtypes smaller than 11 mm in radiological evaluation, although the number of patients in each subtype is relatively small.

Classically, the TNM stage system is used for breast cancer staging (17). Pathological tumor size is defined by the largest tumor size or the largest foci where there is more than one. Following this concept, the largest pathological tumor size either on VAB/EVAB or surgical specimen was used to pathological stage.

In those patients with invasive tumors completely resected by VAB, three (14%) were found to have nodal disease at SLNB, despite negative radiological staging at diagnosis—two luminal A tumors and one luminal B tumor according to immunohistochemical subtyping. All were pT1a/b tumors. Given the increasing use of molecular profiling in identifying patients at genomically low risk despite nodal disease (18), the question remains whether SLNB adds valuable prognostic information in the setting of minimally invasive local treatment or whether SLNB can be safely omitted in this setting.

VAB was a less effective approach for percutaneous resection of DCIS. The largest DCIS completed resected by VAB was 6 mm. DCIS represented just 8 of 29 (27.6%) of all tumors CR and 10 of 47 (21.3%) of PRP compared with 21 of 29 (72.4%) and 37 of 47 (78.7%), respectively, for IC (p 0.001). Additionally, in this series, there were five cases of DCIS, which were upgraded from DCIS to IC following surgery. In our series, lesions presenting with calcifications alone in the absence of an associated mass were much less likely to be completely excised.

Analysis of extent of residual disease following surgical excision allowed the evaluation of VAB for potential minimally invasive resection of breast cancer. In this case series, the procedure was performed with diagnostic rather than therapeutic intent. MRD was defined as ≤ 3 mm of IC/DCIS residual disease in the final excision surgical specimen. This definition was used, because it could therefore be hypothesized that those cases could have been potentially resected in a procedure carried out with therapeutic intent (one or two more core samples); furthermore, focally positive margin is defined as cancer invading for less than 4 mm in length from the inked margin (19), and omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival (20) or the local regional recurrence rate (21, 22) in the context of appropriate adjuvant radiotherapy and endocrine therapy. Although close margins are defined as tumor less than 2 mm width from the inked margin (23), the rate of residual disease on close and focally positive margins is similar (22, 23).

Screening mammography has been associated with reduced mortality from breast cancer in women 40–70 years of age, with absolute risk reduction of 0.809 (0.742–0.833 CI) (24). Benchmarks reported by the Breast Cancer Surveillance Consortium (BCSC) for mammography screening are median size of IC of 14 mm, 77.3% of node negative cancers, 52.6% of minimal cancers (less than 1 cm invasive cancers or in situ), and 74.8% of stage 0 and 1 cancers (25). Most of cancers detected on screening programs are small node negative cancers potentially eligible for percutaneous treatment.

Overdiagnosis in mammographic screening programs remains a significant problem, with reported rates ranging from 11%–22% (24–28). This has largely been attributed to a substantial increase in the detection of small tumors, often with favorable biological features, without any corresponding reduction in the incidence of larger tumors, nor indeed of metastatic disease (26). Local therapy remains an integral part of the treatment of such cancers; however, it is necessary to tailor treatment approaches to the needs and preferences of the individual, minimizing treatment morbidity as far as possible while preserving oncological safety (15). Thus, there is increasing interest using minimally invasive approaches for the local therapy of breast cancer, in part to address the issues around overdiagnosis and consequent overtreatment.

In this context, several percutaneous ablative techniques have been described, with high-technical efficacy rates (> 80%), low complication rates, and acceptable local recurrence rates (10, 29). More recently, interim analysis of the ICE3 prospective, single-arm trial evaluating cryoablation for low-intermediate grade, biologically favorable tumors <15 mm in women aged 60 years or older demonstrated an ipsilateral breast tumor recurrence rate of 2% after a mean follow-up of 35 months (30). For 194 patients, who received successful cryoablation, the mean age was 75 years (range: 55–94 years). The mean tumor length was 8.1 mm (range: 8 mm–14.9 mm), and the mean tumor width was 7.4 mm (range: 2.8 mm–14 mm). Therefore, it appears that ablation techniques may be useful in treating early stage breast cancer, although there is a paucity of high-quality, randomized evidence comparing them with surgery to support adoption into clinical practice. However, ablative techniques by their nature disrupt the tumor and do not provide tissue for evaluation, which is required for histopathological assessment and increasingly for molecular profiling to guide selection of systemic therapies.

Tumor size on image for PRP by VAB was 8.50 mm ± 3.77 (4–25). VAB differs from cryoablation, as cryoablation is an ablative technic, whereas VAB is based on resection allowing pathological evaluation of the specimen.

Another percutaneous excisional technique, which allows histopathological evaluation of tumor margins, is the Breast Lesion Excision System (BLES). The IPEX trial used BLES, which excises the lesion whole rather than piecemeal (31). The IPEX trial reported 124 cases of DCIS or IC, and following excision, 101 (81%) had clear histologic margins [average lesion size was 11 mm for both invasive cancers (4 mm–20 mm) and DCIS (1.5 mm–20 mm)]. However, the BLES device has now been withdrawn from the market, and has not been a widely available technique, unlike VAB technologies that are in common use across the globe.

Inevitably, there are some limitations to a retrospective single-center case series of this nature. Patients were undergoing a diagnostic procedure rather than a therapeutic procedure. Patient numbers are relatively small, particularly in respect of the immunohistochemical subtype analysis, which means that it is difficult to draw definitive conclusions about the ability of VAB to fully excise different subtypes of breast cancer. However, this study adds to the weight of data supporting the potential use of VAB for the treatment of small, biologically favorable screen-detected invasive breast cancers. The ideal evaluation of this technique would require a large, multicenter randomized study such as the UK SMALL trial (10). SMALL is a prospective, multicenter, randomized phase III trial of minimally invasive VAE procedure versus surgery in patients with small (≤ 15 mm), biologically favorable screen-detected breast cancer conducted in NHS, United Kingdom, which is recruiting patients. The aim of the trial is to generate high-quality, practice-changing clinical evidence to support the safe de-escalation of surgical treatment within the context of standard adjuvant radiotherapy and endocrine therapy in selected patients and will evaluate both the requirement for re-excision after VAE and long-term local recurrence rates.

This data provides further evidence that small, low/intermediate nuclear grade pT1a/b breast tumors presenting as a mammographic/ultrasound mass lesion can be potentially completely resected percutaneously by VAE. Prospective trials supporting minimally invasive techniques are required to support evidence-based change in surgical practice.

The original contributions presented in the study are included in the article/supplementary materials. Further inquiries can be directed to the corresponding author.

The studies involving humans were approved by Ethical Committee of Santa Casa de Belo Horizonte by the number 25761019.8.0000.5138. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

All authors contributed to many steps of the research, including study concepts, study design, data acquisition, data analysis and interpretation, statistical analysis, manuscript preparation, manuscript editing and/or manuscript revision. All authors contributed to the article and approved the submitted version.