Short-term and long-term outcomes of breast-conserving surgery in patients with breast cancer: a non-randomized clinical trial

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BACKGROUND

Breast cancer (BC) treatment is one of the key healthcare problems, as BC is the most commonly diagnosed type of tumor among women worldwide [1]. According to the World Health Organization, 2.3 million new cases of BC were reported in 2022, and approximately 670,000 women died of the disease.¹ Over the past decade, a significant amount of data has been collected, reflecting an in-depth understanding of the biology and treatment of early and advanced BC [2]. Due to the widespread use of screening mammography in many countries worldwide and greater access to effective medical treatment, the mortality of BC is decreasing [3]. BC is increasingly detected in the early stages, when breast-conserving surgeries are possible [4].

Based on the fact that the effectiveness of modern treatment of patients with BC should be assessed by the number and quality of years lived, more attention has recently been paid to assessing quality of life indicators [5]. The improvement of surgical approaches enhances quality of life after surgery [6].

This study aimed to assess the immediate and long-term results of using the proposed method of breast-conserving surgery.

METHODS

A non-randomized clinical study was performed to compare the outcomes of patients in the experimental group who received the intervention under study with those of the control group who did not receive it.

According to the Clinical Guidelines of the Ministry of Health of the Russian Federation, the preferred surgical treatment for BC is breast-conserving operations involving the removal of a tumor with a small amount of surrounding healthy tissue (grade of recommendation: A; evidence-based level—1a).² The control group included 194 patients who underwent breast-conserving surgery as part of a combined/multimodality treatment. The therapeutic approach was determined based on the main characteristics of the disease: stage and histological and molecular biological type of tumor growth. Group 1 patients (n = 96, historical control) underwent surgery between 2011 and 2015 and underwent standard breast-conserving interventions. Group 2 included 98 patients who underwent surgery between 2016 and 2020 according to the proposed approach [7].

All patients from the control group were marked in a standing position before the surgery, with a resection margin of ≥2 mm.

Intervention

After two preoperative showers with antiseptic, skin incisions were made along the marking line. Breast tissue was removed along with the tumor, and an urgent histological examination of the resection margins was conducted. The bed of the removed tumor was marked with X-ray positive clips (≥5 pieces) for subsequent visualization of the surgical area with adjuvant radiation therapy [8].

Then, the fiber was isolated in the medial part of the axillary vein, and a biopsy of the sentinel lymph node or regional lymph dissection was performed. The axillary and resection areas were drained using polyvinyl chloride tubes.

Subsequently, the lateral adipocutaneous flap was placed in the axillary region, as close to the nervus thoracicus longus as possible, with free-edge positioning excluding its deformation. Additionally, a similar suture fixation was performed 15–20 mm medial from the initial injection. The surgery was completed by checking hemostasis, excluding foreign bodies, closing the wound in layers, and applying an aseptic dressing.

The volume of lymph dissection was determined based on the involvement of peripheral lymph nodes in the tumor process. Thus, if the results of ultrasound and cytological confirmation showed axillary lymph node involvement, lymphadenectomy was conducted; otherwise, a biopsy of the sentinel lymph nodes was carried out.

Inclusion criteria:

1. Ductal carcinoma in situ (DCIS);
2. BC stage 1: сТ1N0M0; stage 2A: сТ2N0M0, cT1N1M0; and stage 2B: сT2N1M0;
3. BC stage 2A (сТ2N0M0 and cT1N1M0) and 2B (сT2N1M0 and сT3N0M0) after neoadjuvant treatment with partial or complete regression (PR, CR);
4. Absence of BRCA1, BRCA2, CHECK mutations, and any malignant tumors in the first- and second-degree relatives;
5. Absence of an intraductal component according to biopsy data;
6. Absence of tumor at the resection margin;
7. Satisfactory functional status of the cardiovascular, respiratory, urinary, and other systems, allowing for surgical intervention;
8. Patient’s desire for breast preservation;
9. Technical feasibility of performing a breast-conserving surgery;
10. Ratio of tumor size and breast volume is ≤1:8 to avoid pronounced deformity and unsatisfactory cosmetic outcome.

Exclusion criteria:

• Locally advanced, primary inoperable invasive BC (cT1N2–3M0, cT2N2–3M0, cT3N1–3M0, and сT4N0–3M0–1);
• BC stage 2A (сТ2N0M0 and cT1N1M0) and 2B (сT2N1M0 and сT3N0M0) after neoadjuvant therapy with no response (NR);
• Mutations of genes associated with BC or malignant tumors in the first- and second-degree relatives;
• Intraductal component in the biopsy material;
• Paget’s disease;
• Multiple primary synchronous cancer;
• Tumor at the resection margin;
• Inability to perform breast-conserving surgery to achieve clean resection margins and an acceptable esthetic breast shape;
• Pathological microcalcifications extending beyond the tumor node or other signs of widespread intracurrent tumor growth visible on mammography and/or MRI, which prevent the removal of the entire tumor growth zone to achieve a clean resection margin of ≥2 mm and form a satisfactory cosmetic outcome;
• Severe concomitant diseases in the decompensation stage;
• Patient’s refusal of breast-conserving surgery.

Control Group Analysis

The mean age in group 1 was 54.83 ± 0.934 years and 55.704 ± 1.998 years in group 2. The majority of patients (group 1, 70 [72.617%]; group 2, 58 [59.184%]) did not exceed 59 years of age at the time of surgery; this age was the most significant factor for maintaining their quality of life by performing breast-conserving surgeries.

Distribution of Patients Based on Pathomorphological Stage

The majority of patients in the control group were diagnosed with stage 2 BC (group 1, 52.085%; group 2, 51.769%). Nonetheless, breast-conserving surgeries could be performed due to the use of oncoplastic resection technique [9]. Table 1 shows that the groups are comparable in terms of disease stage (χ² = 0.722).

 

Table 1. Distribution of patients by primary tumor histology in the study groups

Histologic tumor type	Subgroup 1 (n = 96)		Subgroup 2 (n = 98)
	Absolute number	%	Absolute number	%
Invasive of no special type	52	54,17	50	51,02
Invasive lobular	29	30,21	35	35,71
Other	15	15,63	13	13,27
Total	96	100	98	100

Note: χ² = 0.722; p > 0.865.

 

The histological and biological types of the tumor were evaluated in the compared groups to determine the need for neoadjuvant therapy. Table 1 presents the distribution of patients by primary tumor histology in the study groups. Quantitative data from two independent groups were used for the analysis.

The predominant histological type of BC was invasive cancer of no special type, followed by invasive lobular cancer. The number of patients in groups 1 and 2 was compared. Based on the histological type of the primary tumor structure, the studied groups were comparable (χ² = 0.722).

Table 2 reveals the distribution of patients according to the biological subtype of the malignant tumor. Quantitative data from two independent groups were evaluated.

 

Table 2. Distribution of patients by primary tumor subtypes

Biological subtype of cancer	Group 1, n = 120		Group 2, n = 79
	Absolute number	%	Absolute number	%
Luminal A	47	48,96	51	52,04
Luminal B	34	35,42	35	35,72
Other (HER2+, basal-like)	15	15,66	12	12,24
Total	96	100	98	100

Note: χ² = 0.491; p > 0.783.

 

The analyzed groups were predominated by luminal A subtype of tumor growth: 47 (48.96%) in group 1 and 51 (52.04%) in group 2. These indicators are comparable with published data on the distribution of histological subtypes of tumor growth [10]. Table 2 shows that the groups were comparable in biological subtypes of the primary tumor (p > 0.783).

All the study patients were treated according to the main characteristics of the disease: the stage and histological and molecular biological type of tumor growth.

The key criteria when choosing surgical access for performing breast-conserving surgery were the size of the breast and tumor (indicating the quadrant and affected area). When the appropriate resection method is selected, preoperative mapping is the key to achieving a good esthetic outcome of surgical treatment and patient satisfaction [8].

The patients were asked to complete the Breast-Q questionnaire prior to surgery and 6 months after the treatment.

All statistical estimates were performed using Statistica 10.0. Statistical analysis of the obtained data was conducted using the parametric (Student’s t test) and nonparametric (Mann–Whitney test, chi-squared test [χ²], and Fisher’s exact test) methods. The significance level was set at р < 0.05.

RESULTS

The main parameters of surgical intervention, including the volume of lymph dissection, duration of surgery, and volume of intraoperative blood loss, were analyzed to assess the immediate results of treatment in the control group patients.

The drains were removed when the lymphorrhea was ≤50 ml, and no later than 7 days after surgery.

The results of treatment of control group patients after breast-conserving surgeries were investigated. The median follow-up was 39 months (IQR: 25–75 percentile) in the study group and 45 months (IQR: 25–75 percentile) in the control group.

Figure 1 shows the indicators of disease-free survival in the control subgroups.

 

Fig. 1. Kaplan–Meier curves for disease-free survival in groups 1 and 2.

 

The 5-year disease-free survival rate in group 1 was 87.14% and 89.74% in group 2. The event-free survival curves in the compared groups did not significantly differ (log-rank = 0.465; p = 0.642; 95% confidence interval: 83.3%–95.5%). The relapses and progression of the disease required treatment adjustments in group 1 patients (Table 3). Quantitative data from two independent groups were evaluated.

 

Table 3. Distribution of patients by treatment for disease progression and recurrence

Treatment options	Group 1 (n = 96)	Group 2 (n = 98)
	Absolute number	Absolute number
Surgical intervention combined with systemic therapy	6	8
Systemic treatment only	5	2
Integrated approach with radiation therapy	1	0
Total	12	10

Note: χ2 = 2.143; р = 0.709. Fischer’s exact test: р = 0.501 (differences are not significant). The odds ratio was 1.257 (95% confidence interval: 0.514; 3.074).

 

The probability of receiving treatment in group 1 was 1.26 times higher than in group 2; however, the 95% confidence interval includes 1, which confirms the absence of statistically significant differences.

The 5-year survival rate in group 1 was 94.71% and 96.74% in group 2 (95% confidence interval: 91.3%–99%). Figure 2 indicates that the survival curves in the comparison groups also did not differ (log-rank = 0.74; p = 0.458).

 

Fig. 2. Kaplan–Meier curves for overall survival in groups 1 and 2.

 

The second Breast-Q questionnaire was conducted at 6-month follow-up, a point which, according to the published data, is the endpoint of esthetic outcome assessment [11]. Each of the questionnaire scales could be used separately [11].

CONCLUSION

The developed method, “Choosing the extent of surgery for patients diagnosed with BC” (database filing code no. “2017621168”, dated October 9, 2017), applied in group 2 contributed to a significant decrease in the incidence of class 1 and 2 surgical wound complications compared to group 1 receiving standard treatment, with comparable long-term outcomes.

ADDITIONAL INFORMATION

Author contributions: O.A.E.: conceptualization, formal analysis, supervision; K.O.I.: conceptualization, supervision; T.M.V.: data curation, writing—review & editing, supervision; B.A.V.: data curation, writing—original draft, writing—review & editing. All authors approved the version of the manuscript to be published and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: The study was approved by the Local Ethics Committee of the Samara Regional Clinical Cancer Hospital (Minutes No. 14 of August 02, 2010). All participants provided written informed consent prior to inclusion in the study (on the day of admission).

Informed consent: The authors have obtained the written informed consent of the patient [and/or the patient’s legal representatives] to publish personal data. The scope of the published data was approved by the patient.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: The work was created using fragments of the author’s previously published text ([EDN: JQYMIV], distributed under the terms of the CC-BY 4.0 license).

Data availability statement: The editorial policy regarding data sharing does not apply to this work, as no new data was collected or created.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer review: This paper was submitted unsolicited and reviewed following the standard procedure. The review process involved three external reviewers, a member of the editorial board, and the in-house scientific editor.

 

¹ World Health Organization (WHO): Breast Cancer, 2024 Available at: https://www.who.int/ru/news-room/fact-sheets/detail/breast-cancer Accessed on January 6, 2024.

² The Gold Standard in Diagnosis and Management of Breast Cancer, 2021 Available at: https://cliniclancette.ru/docs/KR_ROOM_2021.pdf Accessed on: November 7, 2024.

About the authors

Andrey E. Orlov

Samara regional clinical Oncology dispensary; Samara State Medical University

Email: OrlovAE@samaraonko.ru
ORCID iD: 0000-0001-6145-3343
SPIN-code: 8902-5712

MD, Dr. Sci. (Medicine), Head, Depart. of Public Health and Health Organization of the IPO, Chief Physician

Russian Federation, Samara; Samara

Oleg I. Kaganov

Samara regional clinical Oncology dispensary; Samara State Medical University

Email: okaganov@yandex.ru
ORCID iD: 0000-0003-1765-6965
SPIN-code: 2705-4187

MD, Dr. Sci. (Medicine), Professor, Head, Depart. of Oncology, Deputy Chief Physician

Russian Federation, Samara; Samara

Maksim V. Tkachev

Samara regional clinical Oncology dispensary; Samara State Medical University

Email: m9277477577@mail.ru
ORCID iD: 0000-0002-4183-0647
SPIN-code: 9681-0358

MD, Dr. Sci. (Medicine), Assistant Lecturer, Depart. of Oncology, Oncologist

Russian Federation, Samara; Samara

Artyom V. Bukin

Samara State Medical University

Author for correspondence.
Email: aarbukin@yandex.ru
ORCID iD: 0009-0008-8083-2689

6th year student

Russian Federation, Samara

References

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