Oncoplastic surgery for the conservative treatment of breast cancer in Perú’s National Cancer Institute

Background Oncoplastic surgery for breast cancer (OPS) has been a surgical trend for the past 25 years. In 2012, OPS has been introduced as the standard treatment for a selected group of patients at the National Cancer Institute of Peru (INEN). The aim of this study is to describe our findings. Methods This is a retrospective and descriptive study that identified demographics, tumour-pathologic features and includes patients solely treated since diagnosis until late follow-up at INEN. These OPS patients were identified from the conservative treatment patients group by review of medical charts and creation of a database for periods December 2005 through December 2015. Results A total of 146 patients were ruled in by the inclusion criteria. All patients were Peruvian females, 56.2% being 51 or older. 93.8% had core biopsy diagnosis of breast cancer and 52.1% located at the upper outer quadrant. 79.5% patients had upfront OPS and the round block (43.2%) and reduction/mastopexy (23.3%) were the most used techniques. pT2 was the most frequent size (54.7%). We achieved negative margins in 134 patients (93.2%) in a single procedure. Of 29 patients, who had neoadjuvant treatment, 11 achieved pCR. Only 5.5% had pN2 or higher. 95.2% received complimentary external beam radiotherapy. Conclusions OPS has proven to be a reliable surgical option, both for aesthetic and oncologic outcomes. Important points for achieving these results are breast surgeons having properly trained under the OPS philosophy and knowing the patients’ characteristics for correct technique selection.


Background
Breast surgical oncology has three major precedents in which the European influence has played an important role. In 1878, Halsted travelled to Vienna to learn from the most famous surgeon in Europe, Theodor Billroth [1]. Back in Baltimore, he perfected and popularised 'the complete method' obtaining better results than his teacher, reporting 50 breast cancer (BC) surgical cases with only three recurrences, giving way to 'Halsted's radical mastectomy' from 1894 onwards [2].
During the 1970s, Fisher in USA [3] and Veronesi in Italy [4] set the second precedent when exploring other treatment possibilities besides Halsted's dogma and showed that breast conserving surgery with complimentary whole breast radiation (BCT) had comparable overall survival (OS) and disease-free survival (DFS) versus mastectomy. There was no added benefit in cutting more, so the BCT tendency started [5]. However, BCT still remained as a partial mutilation where asymmetries and deformities were not considered relevant as oncological results were more important than psychological and aesthetic damages. Plastic surgeons developed different ways to handle breast aesthetic problems and soon started using reduction mammoplasty techniques to reshape and reconstruct some BCT cases [6][7][8] and published different approaches for them [9].
The third event started in 1993 when Galimberti (plastic surgeon) and Veronesi (surgical oncologist) reported a case series in Milan for centrally located tumours where the remodelling of the breast followed the oncologic resection, obtaining acceptable aesthetic results in a single operating day [10]. Audretsch coined the term 'oncoplastic surgery' (OPS) for them and it is a surgical philosophy that merges plastic surgery techniques with oncologic clear margins and has gained global acceptance for the satisfaction of patients and their treating surgeons [11]. The French group led by Clough consolidated OPS as a third surgical option for breast surgeons besides BCT or mastectomy. They classified BCT preventable sequelae [12] and developed technical recommendations for OPS by quadrants of the breast. They made it clear that it is a new surgical option for which breast surgeons may receive specialised training [13].
The OPS philosophy was introduced to Latin American countries through specialisation courses led by the Spanish Benigno Acea [14]. Peruvian breast surgeons were no exception. Between 2012 and 2015 breast surgeons including residents and fellows from the National Cancer Institute of Peru (INEN) attended the courses taught by Acea and adopted OPS as a surgical standard for selected patients since 2012. The aim of this study is to analyse a subset of patients treated with OPS in the period 2005-2015 at INEN.

Methods
From December 2005 until December 2015, more than 1,200 breast conserving surgeries were performed at INEN. We retrospectively reviewed medical charts and built a database for OPS cases. Demographics, tumour characteristics, technical aspects of OPS, axillary surgery, adjuvant therapy, follow-up, and outcomes were collected. We processed information with SPSS v.22 through frequencies, percentages and measures (median, mean and range). Surgeries were carried out exclusively by the breast surgical oncology staff, residents and fellows at INEN properly trained under OPS philosophy. We included patients with confirmed BC diagnosis treated by OPS and received neoadjuvant or adjuvant systemic treatment and excluded patients with bilateral tumours, metastatic disease at diagnosis, patients with inflammatory carcinoma, patients with treatment in a previous institution (surgery, chemotherapy or radiation therapy), patients with incomplete data on medical charts and those lost at sight for more than 6 months in the follow-up appointment. Staging by American Joint Committee on Cancer 7th edition.

Results
In total, 146 patients met our inclusion criteria. All patients were Peruvian women, where 56.2% of cases were >50 years old. Almost 90% of the cases were diagnosed with biopsy at INEN. About 70% had no co-morbidities. In 52.1% of the cases, the tumour was located at the upper outer quadrant (UOQ), while the least affected was the lower inner quadrant (LIQ). 73.9% of cases had clinically tumours >2 cm (cT2) and 73.6% of cases had clinically negative axilla (cN0). Core biopsy made diagnosis for 93.9% of cases and the rest had fine-needle www.ecancer.org ecancer 2018, 12:815 aspiration (FNA) and cytology, both on an outpatient basis in the clinic. We found 11 in situ (10 Ductal carcinoma in situ (DCIS), 1 Lobular carcinoma in situ (LCIS)) cases in core biopsies but final operative specimen showed nine cases to have infiltrating component. Molecular profiles by immunohistochemistry (IHC) markers were performed in all the core biopsies and in some operative specimens, making a total of 144 analysed infiltrating carcinomas. Luminal A was most frequent (42.2%) and Triple Negative (TN) is less frequent (9%) ( Table 1).
OPS cases were divided into two periods showing only two cases which met our inclusion criteria between 2005 and 2011, whereas the vast majority of OPS was concentrated between 2012 and 2015 with 144 cases. OPS techniques were selected by surgeon discretion depending on the breast size, primary tumour location and level of complexity of the technique ( Table 2). Level II techniques were used in all the cases. We identified seven OPS techniques. The most frequent OPS technique was Benelli's round block ( Figure 1) performed in 63 patients (43.2%), followed in frequency by Vertical Mammoplasty (reduction/mastopexy) in 34 cases (23.3%). The Lateral pattern with recentralisation of the nipple-areola complex (RNAC) was an interesting tool for laterally located tumours ( Figure 2) and was used in 31 patients (21.2%). Same day symmetrisation of the contralateral side by plastic surgeons was possible in 18 patients (12.3%). Pathology showed that pT2 was the most frequent size (55.4%). 29 cases received neoadjuvant systemic therapy and 11 of them (7.4%) achieved pCR, 5 of which were TN (41.5%), 3 Luminal B (27.3%), 2 Luminal A (18.2%) and 1 case of HER 2 (9.1%).

Figure 2. Lateral with re-centralisation of NAC. (A) Preop. Markings of lateral pattern with RNAC (solid line), frontal view. (B) Preop. markings of tumour (dotted line), side view. (c) First day postop, frontal view (with PRD). (D) First day postop, side view (with PRD).
In two cases (1.4%), the operative specimen showed DCIS in the form of mass >2 cm and other >5 cm. One invasive ductal carcinoma (IDC) case that was diagnosed by incisional biopsy showed no residual disease in the final operative specimen. www.ecancer.org ecancer 2018, 12:815 We achieved negative margins in 134 patients (93.2%) in a single procedure. Margins could not be defined in 12 cases given that 11 of them had pCR and 1 had incisional biopsy as described. In 124 cases (84.9%), negative margins were obtained after palpable tumour resections. The remaining 10 cases (6.8%) had positive margins, requiring a second surgery with final pathology free of malignancy. No patients had to return to the OR for complications.

Discussion
BC incidence is rising globally [15]. Latin American countries like Peru are no exception. The population-based cancer surveillance system of Lima for the period 2004-2005 showed age-adjusted incidence rate (AAIR) of 33.8 cases per 100 thousand women [16], with 3,065 incident cases (only 5.6% of DCIS cases versus USA where DCIS reaches 20-25% [17]). For the period 2010-2012, the registry showed 6,413 incident cases with an AAIR of 40.9 cases per 100 thousand women [18]. Perú´s INEN is located in Lima and records between 2006 and 2015 showed an average of 1,231 new BC cases per year [19].
Since the 1990s [10,20], the evolution of reconstructive surgical techniques started focusing on BCT deformities [12] and gave way for coupling mammoplasty techniques (during the resective operation) for preventing sequelae using Benelli´s round block [6,7], vertical patterns like reduction/mastopexy [8], common sense surgical approaches for hidden scars [21] and knowledge about applications and limits of them [14]. All of these contributions have shaped the OPS philosophy to a standarised mapping of the breast by prone-deformity territories and proposing the best OPS technique by tumour/quadrants locations [13,22,23]. Even with the well-known utility from neoadjuvant treatment applied to BCT [24,25], we have avoided resorting to mastectomy and used OPS with presentations like locally advanced disease (taking into account the tumour biology) if a favourable response is achieved and breast conservation can be maximised at its best [26].
Numerous proposals have expanded the OPS range of techniques in the literature [27][28][29][30][31][32][33][34][35][36][37][38][39], but it is important to highlight the factors that guide them to success: (a) The surgeon must be trained under the OPS theoretical-practical model [40] to understand the importance of breast anatomy and pedicles used by plastic surgery, breast segments proposed by Acea [22] and according to the complexity levels (I-II) proposed by Clough for a proper technique selection that suits the patient and the glandular density of the breast [13,41,42].
(b) The patient must understand the benefits, risks and alternatives of OPS so that they may provide informed consent [43]. This includes an understanding of the co-morbidities and other risk factors like smoking or diabetes [23].
Rietjens et al [44] calculated the volume of the operative specimen by multiplying length, width and height. Volume was considered by Garces et al [45,46] and demonstrated that in spite of higher volumetric resections, OPS achieved excellent aesthetics as well as fewer re/excisions for positive margins.  An abstract presented at the annual meeting of the American Society of Breast Surgeons 2017 as a poster by the present article's authors showed a low number of complications (similar to published literature) for seven OPS techniques performed for both benign and malignant diseases [47]. However in our study, the number of complications was not obtained. We estimate that complications such as seroma, haematoma, dehiscence, and wound infections arose in less than 10% of the cases and were managed on an outpatient basis.
The oncological long-term results of a subgroup of patients in our database are very encouraging with DFS and OS comparable to BCT [48].

Disadvantages of the study
The 2005-2015 period showed more than 1,206 breast-conserving surgeries in medical charts, of which 806 patients were operated on due to a BC cause. More than 300 cases underwent OPS for different reasons. However, some patients who had received resective surgery previously at another institution with OPS techniques or patients who required complimentary surgery for re-excision or axillary staging were operated on using the OPS approach at INEN, therefore being excluded by our criteria from the study. We also excluded other patients with final pathology reports showing benign tumours (benign Phyllodes, breast lipomas, complex cysts and papillary breast tumours), other malignant non-carcinoma (breast carcinosarcoma) BC, but where the surgical report had missing information about the OPS technique. It is essential to have a standardised perioperative order for the registry of data on clinical charts as well as a surgical report detailing the OPS technique. The technical OPS aspects must be respected to avoid losing valuable information, as well as to report complications in the postoperative follow-up. www.ecancer.org ecancer 2018, 12:815

Conclusions
OPS techniques are a new challenge for breast surgeons. Training and proper patient selection are key to maximise aesthetic and oncologic results for the satisfaction of both patients and surgeons.

Conflicts of interest
None of the authors has any financial interests to disclose. www.ecancer.org