Comparison of the Cosmetic Results, Quality of Life and Patient Satisfaction Achieved With Round-block and Retroglandular Oncoplastic Breast Conserving Surgeries

Introduction In the last four decades of oncological breast surgery, based on Umberto Veronesi and Bernard Fisher's prospective comparative studies, organ conservation became highly significant in the case of early breast cancer with the application of microscopically negative surgical margin and adjuvant whole breast irradiation (WBI), which is proven to offer the same survival chance as mastectomy.\[1,2\] However, in practice, the apparent benefits of organ conservation shaded by the need of second surgery, 5-30%, (repeated directed re-excision or mastectomy) due to microscopically positive surgical margins; the 3-5 weeks long, logistically demanding radiotherapy; and the cosmetically impaired or distorted breasts that remains almost 30% of the surgeries. \[3-5\] The latter can be explained by our published previous prospective study that the patients report significantly intolerable cosmetic results after 10% volume loss from the inner quadrants and approximately 15-20% volume loss from the lateral quadrants, when its associates with adjuvant WBI. \[6\] Aside from volume reduction, during a traditional breast conserving surgery (BCS) the tumor bed is left behind as a cavity, whose posterior wall is composed of the pectoralis major muscle and the pectoral fascia, while its anterior wall is composed of skin. Already in the early postoperative stage, with the removal of the seroma, the skin retracts and adheres to the breast muscles or to the fascia. This process is accelerated by the irreversible of the complete residual parenchyma and the change of the skin's structure, elasticity and microcirculation during WBI. This could result 10-20% shrinkage of the breast. The breast shows a typical deformity with the directly curved incision line above the tumor as a result of secondary wound healing process mentioned above. Compared to the contralateral side its volume shrunk, the nipple dislocated to the axillary fold due to the adhesion of the upper-outer quadrant in case of this quadrant's volume loss and typical bird beak formation occurs in case of lower quadrants' border excision; while a central excision usually results in a so-called doughnut shaped breast with a central retractation. Additional challenge is the reconstruction of the post-BCS breast because it is more complicated and achieves poorer cosmetic results than the post-mastectomy breast construction. \[7\] In order to prevent the above listed disadvantages of BCS, a sophisticated organ conservation breast-surgery was developed with the adaptation of plastic surgery techniques in the last decade, which was named Oncoplastic Surgery (OPS) by Werner Audretsch. \[8\] These surgeries are volume reducing breast lift surgeries or their alterations, which are based on the knowledge of breast anatomy - especially on its blood circulation (e.g. Würinger's Septum), and its structural and aesthetic subunits (e.g. inframammary fold (IMF), nipple and areola complex (NAC)). The surgeries require particular plastic surgery knowledge. The OPS based on volume displacement using and mobilizing the glandular pillars to fill the wound cavity using the advantages of breast ptosis, narrowing the overall base diameter and the "footprint", and repositioning the NAC, which left behind after the radical removal of the tumor. The OPS is suitable to perform real quadrantectomy, even with a better aesthetic result then it is preoperatively. According to each segments of the breast, various oncoplastic techniques can be applied, giving the oncoplastic surgeon an unprecedented freedom to offer a personalized solution. The OPSs can be classified based on their technical complexity or on the level of volume (\<20% / 20-50%) needed to be replaced (Level I./II.). \[9\] Following the OPS, the remaining scars caused by radiation become almost invisible, and due to the lack of wound cavity, adhesion does not occur.

The most popular Level I. oncoplastic techniques are the periareolar or round-block techniques, or retroglandular technique, which was first published in the international literature by the current authors. These techniques are for those malignant tumors (cT\< 3cm) which could be possibly located centrally in every quadrant and requires wide surgical excision less than 20% of the entire breast. \[10, 11\] The literature relied on oncoplastic breast conserving techniques is usually limited to retrospective cohort studies, while its prospective randomized comparison with traditional breast conserving surgery cannot be performed due to ethical reasons.

The purpose of the current clinical study is to scientifically analyze and compare the clinical, oncological and aesthetic results of the standardized oncoplastic breast conserving surgical techniques, round-block versus retroglandular, in one center for unilateral, solitary, malignant breast tumors in a responsive-adaptive (RAR) prospective randomized trial with long term follow-up.

Aim of the study The aim of this clinical study is to analyze due long term follow-up, the clinical, oncological, aesthetic results and patients' reported quality of life and satisfaction in a responsive-adaptive (RAR) \[12\] prospective, randomized study at a large number of patients whom receive round-block and retroglandular oncoplastic breast conserving surgeries.

According to the study's hypothesis, breast conserving surgery can be oncologically successful and safe with low complication rates resulting in high rate of patient satisfaction and good quality of life, which can be maintained for a long time after WBI with the application of modern oncoplastic breast conserving surgeries. We assume in this study that against of the earliest and mostly studied round-block oncoplastic surgery, the retroglandular technique, firstly reported in the literature by the current authors, is also adequate for oncologically safe, radical tumor removal that comes with low complication rates, suited for adjuvant treatments and able to offer better cosmetic results (NAC does not distorted, and pathological scar will not develop) than round-block OPS and high rate of patient's satisfaction that can be maintained for long-term.

Patients and method The participation in this study is voluntary. In this current response-adaptive (RAR) prospective randomized study the applied surgical operations count as routine interventions in the literature, as much as in our Department, with standardized techniques. The applicable round-block and retroglandular oncoplastic breast conserving surgeries do not mean new surgical procedures for the patients, not in their techniques, nor in their indications; the prospective examination serves only as a guarantee for the quantitative and qualitative data collection. The examination does not influence the applied oncological therapies; those are still executed based on the institution's preoperative and postoperative multidisciplinary breast oncological committee's professional decisions.

The study does not change the complex oncological treatment in any ways, considering the NCI protocol.

In this study the response-adaptive classification means that the choice of the optimal surgical procedure for the patient is not influenced by the clinical study. The decision making model is the same as it is in our department, same as for patients that are not participating in the study, so the subgroups chosen according to the oncological morbidity, the location of the tumor (the round-block technique is more appropriate for those ones that are closer to the surface, while the ones located more deeper, closer to the pectoralis major muscle are adequate for the retroglandular procedure), the breast size, the structure and ptosis of parenchyma. The applied and studied surgical techniques like aside of the clinical examination, do not require symmetrization.

The current study does not include intervention in a scientific term due to the above listed reasons, so it is not differs of the routinely used treatment protocol.

The primary endpoint of the study Correlation analysis of oncological control, cosmetic result, patients' satisfaction and quality of life achieved by various surgical techniques; and these follow-ups in one, two, three, four, and five years.

The study's secondary endpoints To determine the complication's ratio of early and late surgeries, and the surgical strain (the length of the surgery and hospitalization).

Based on the results, once it gains scientific confirmation, the retroglandular, oncoplastic breast conserving technique, proposed by the authors for the first time, could become a Level I oncoplastic technique.

Patients:

\- Under the age of 65, suffering from unilateral (cT\< 3cm) in situ or invasive breast cancer, who are fit for breast conserving surgeries, who had no previous breast surgery, independent from axillary surgery (sentinel lymph node biopsy or axillary block dissection)

Excluding factors:

* In case the patient does not volunteer for the examination or the follow-ups * Age above 65 years or poor general health condition, where the estimated life expectancies would be less than 2 years even without a tumor * Malignant invasive tumor in the past history (except for non-melanoma skin tumors) * Mastectomy performed due to positive resection margin * Prior breast surgery (e.g. aesthetic surgery, breast lift) and/or radiotherapy on the breast or in the axilla * Malignant tumor is not removed completely with pathological examination * Severe non-surgical (e.g. radiotherapy) complication, which could influence the aesthetic and functional results * Autoimmune diseases * Tumor requiring mastectomy, or clinically larger than 3 cm tumor primary, or mastitis carcinomatosa, lymphangitis carcinomatosa * Long-term steroid usage, which changed the skin's quality and structure * Patient under foster care, or psychically non-cooperative patient

Preoperative examinations:

* Physical examination * Triplet examination of the breast * Preoperative core biopsy or FNAB * Staging examinations: chest x-ray, abdominal ultrasound, bone scintigraphy * Axillary ultrasound and cytological examination if required * Required additional imaging based on the oncological staging (targeted x-ray, CT, MRI, PET) * Routine hematological and blood test analysis * Measurements of jugulum-nipple width, nipple midline width, and nipple inframammary-fold width * Measurements of the areola's horizontal and vertical diameter * Regnault Classification of breasts' ptosis * Photo documentation (standard 5 directions and ap with raised arms) and the application of the BCCT.core program (regarding data protection regulations) \[13\] * Filling out the BREAST-Q questionnaire \[14\]

Recorded data:

Age, body mass, height, BMI, pre-/postoperative cup sizes, presence of preoperative breast assymetry and its severity (BCCT.core software data), past history, medication, smoking habits, oncological data, cTNM, pTN, pathological data, molecular genetic subtype, neoadjuvant and adjuvant therapy, type of axillary treatment, locoregional cancer recurrance, metastasis.

Postoperative complications were classified following Clavien-Dindo Classification\[15, 16\] Grade I complication (light inflammations, non-surgical haematoma or suffusion, seroma formation, partial skin/NAC loss, limited fat necrosis, SSI and lymphoedema) does not require medication or surgical treatment. Grade II complication is a Grade I complication that requires medication or surgical interaction (antibiotic therapy, resuture due SSI and multiple puncture due chronic seroma). Grade III complication requires invasive surgical action (haematoma evacuation, chronic inflammation which requires reoperation, severe fat necrosis, full skin/ NAC necrosis and wound dehiscense). Grade IV complication means temporary organ failure. Grade V complication is one that leads to death.

The following data are collected in this trial: preoperative jugulum-nipple width,

• Complication's ratio [Срок оценки: 5 years follow up]