Breast cancer disease and treatment methods not only affect patients’ physical functions, but also bring significant impact on patients’ psychological and social consciousness. In terms of psychological and social consciousness, how can patients get through the psychological crisis, overcome the adverse emotions such as fear, depression and anxiety, and successfully complete all treatments; how to establish good relationship with family members, receive family support and regain normal family life order; how to strive to return to society, establish good interpersonal relationships, regain work and realize their own value.
It can be said that breast cancer therapeutics research is a paradigm of cancer treatment research, and surgery, radiotherapy, chemotherapy, endocrine therapy and biological therapy all have a considerable place in breast cancer treatment. In terms of surgical treatment, for example, the classical Halsted radical surgery for breast cancer laid the foundation for the emergence and development of the concept of radical cancer treatment; the emergence of modified radical surgery for breast cancer provided new research ideas for functional preservation of cancer treatment; breast cancer treatment with breast preservation has revolutionized cancer treatment and transformed cancer treatment from a single anatomical-biological model to a social-psychological-biological model. It has transformed cancer treatment from a single anatomical-biological model to a socio-psycho-biological model .
The surgical treatment of breast cancer has undergone four major journeys: radical surgery, extended radical surgery, modified radical surgery, and breast-preserving surgery, forming today’s individualized specifications for both extended and reduced surgery, and for both cure and quality of life. In addition to patient factors, the rational choice of treatment strategy for breast cancer must avoid the stereotype of “each doctor for himself”. In other words, surgeons, radiologists or physicians only pay attention to the indications of their own treatments, but ignore the rational design of the overall treatment plan and the organic combination of each treatment, which is forbidden in modern therapeutics.
With the intensive basic and clinical research of breast cancer, the treatment strategy has changed significantly, for example, both classic surgical works indicate that inflammatory breast cancer is a contraindication to radical mastectomy. Today, with the use of rational preoperative chemotherapy and radiotherapy, radical mastectomy has played a positive role in improving long-term survival and quality of life.
As a clinical worker in breast cancer, whether as a surgeon, radiotherapist or internist, when treating each case of primary breast cancer, one should not only complete the implementation of the treatment tools that one has, but also, more importantly, make a reasonable overall treatment strategy for the patient. In this way, each patient can receive the most appropriate and reasonable treatment and obtain the best prognosis.
Histologically, breast cancer is divided into two categories: invasive and non-invasive. Non-invasive carcinoma, also known as breast carcinoma in situ, includes intraductal carcinoma and lobular carcinoma in situ. It is important to emphasize that the definition of “early breast cancer (EBC)” is not entirely consistent between pathologists and clinicians, as pathologists are interested in the histogenesis of cancer and the difference between some so-called precancerous lesions and carcinoma in situ.
The term EBC includes only intraductal carcinoma, lobular carcinoma in situ and microscopic early invasive carcinoma with only punctate invasion of the basement membrane (see the relevant section for details of treatment strategies for histologic EBC). Clinicians, on the other hand, are concerned with the prognosis of the cancer from a clinical perspective. The term EBC does not necessarily mean the initial stage of the disease, but rather a group of “highly curable” diseases with no or few lymphatic metastases. In this sense, clinicians refer to EBC not only as intraductal carcinoma and lobular carcinoma in situ, but also as part of the TNM stage I cases.
Thus, in the literature, including classic professional works and journals and magazines, the term “EBC” is applied very irregularly, and only after reading the contents carefully can we find out the specific connotation of “EBC” in specific articles. Some EBC connotations refer only to true histologic EBC; some EBC connotations extend to clinical stage I and up to stage II.
Therefore, it is recommended that the term “EBC” should only be applied to histologic early-stage cancers, and that the term “clinical EBC” should be used if early clinical stage breast cancer is included. The term “operable breast cancer” means a breast cancer that is confined to a local-regional area (confirmed by current clinical examination methods) and can be surgically removed “radically”. In the literature, it generally refers to cases of breast cancer before clinical stage IIIA.
The authors attempt to discuss the treatment strategy of breast cancer.
I. Reflections on clinical practice
1. Sense of mission
The biological function of the breast is lactation, the lactating organ, and lactation is the fountain of life that allows human beings to continue. On the other hand, breast has an irresistible position in human aesthetics. Breast is one of the second sex characteristics of women, and is the symbol of female beauty, representing the breath of life, youthful vitality, love and power, and is irresistible to human nature.
From the statue of the goddess Venus in the 4th century BC to modern paintings, theater and movies, urban art sculptures, etc., all are trying to show off the value of breasts in human beauty. However, women’s breasts are also a “disaster-prone place”, with many diseases attacking them, especially breast cancer, which has become a common and frequent disease that seriously affects women’s physical and mental health and even threatens their lives.
The incidence of breast cancer is increasing by 0.2% to 8% worldwide each year, and the fastest increase is in developing countries including China. The absolute number of patients who lose their breasts and their lives to breast cancer is increasing every year. This shows how important the task of breast cancer prevention and treatment is.
From the perspective of preventive medicine, what we can do to prevent and treat breast cancer is still limited to clinical work (secondary and tertiary prevention), and the etiological prevention of breast cancer (primary prevention) is almost limited to the stage of “paper work”. This is because
(1) The etiology of the majority of individual breast cancer patients is unknown. Because the etiology of the majority of breast cancer patients is unknown, targeted prevention is difficult to obtain. And the major known risk factors are practically unmodifiable such as increasing age, young age at menarche, late menopause, and older age at first pregnancy. Potentially modifiable risk factors include endogenous hormone levels, obesity, exercise, hormone replacement therapy, alcohol consumption, breastfeeding, oral contraceptives, and dietary profile, but the easier the modifiable risk factors are, the more limited the overall prevention of breast cancer. Fertility factors are governed by many factors; lifestyle, psycho-psycho-endocrine factors, increasing human work pressure, rising family burden, instability of marital status, etc. globally today are also difficult to shift by human will.
(2) 5-10% of breast cancer patients are related to genetic factors. About 50% of women who develop breast cancer due to genetic factors have mutations in the BRCA1 or BRCA2 genes. However, humans have no choice about genetic and physiological factors, and they have no initiative about the gene carrier status at birth; meanwhile, as far as the current status of research is concerned, endocrine chemoprevention studies of tamoxifen (triamcinolone, TAM) and raloxifene (Raloxifene)] for the prevention of breast cancer in high-risk groups are far from the stage of clinical utility.
Bilateral prophylactic mastectomy (BPM) can reduce the risk of breast cancer in BRCA1 or (and) 2 mutation carriers by 85% to 90%, and if BPM is performed on BRCA1 or (and) 2 mutation carriers at age 30, it can extend life expectancy by 3 to 5 years, but for BRCA mutation carriers > 60 years, it can extend life expectancy by 3 to 5 years. However, there is no significance for BRCA mutation carriers aged >60 years.
In the face of the increasing incidence of breast cancer and the slow progress of breast cancer prevention measures, it is particularly important to implement the best treatment strategy for breast cancer patients.
2. Changes in treatment paradigm
In the 21st century, the treatment paradigm of breast cancer has undergone significant changes, as follows
(1) The concept of individualized treatment is generally accepted;
(2) Evidence-based medicine is the basis for guiding individualized treatment;
(3) The scientific and technological content of treatment methods is constantly improving;
(4) The position of various therapeutic tools in the comprehensive treatment is changing rapidly. However, in the course of our medical practice, what disease, like cancer, is so blinded by adjuvant therapy! That is, the percentage of innocent recipients of treatment is far greater than the true beneficiaries! How to screen the high-risk group for treatment failure and rationalize the target population for treatment to the maximum should still be the top priority of clinical research work!
3.Individualization concept
(1) The international “individualization”
The incidence rate of breast cancer in the United States was 110.6/100,000 at the end of the 20th century, while the incidence rate of breast cancer in China was about 20/100,000, with the highest rate of 56.2/100,000 in Shanghai.
②Differences in age of high incidence: In the United States, about 25% of breast cancer patients are first diagnosed before menopause; in China, the incidence of breast cancer begins to rise at the age of 30, with a peak age of 40-49, 10-15 years earlier than in western countries, and premenopausal cases account for more than 60%.
(3) Ethnic differences: There are certain differences between different ethnic groups not only in terms of anatomy and physiology such as body mass and breast size, but also in terms of molecular biology expression. For example, the incidence rate of genetically related breast cancer is different between East and West, and the expression level of hormone receptors is different. The ER positive expression rate of breast cancer in Chinese women is 60.5% [9], while most of the western countries report >70%.
④ Differences in the distribution of disease stages: Stage III and IV cases still account for about 30% of the first diagnosed patients in China, while only 15% in the United States during the same period. However, this situation is improving.
(2) Individualization among populations: The biological characteristics of breast cancer are obviously individualized, and the concept of “individualized treatment” must be implemented in medical practice in order to achieve maximum humanization in medical practice.
(1) Spatial individualization: The non-synchronous nature of the tumor cell cycle determines that the proportion of cells in the S-phase of the tumor cell population varies significantly at any point in time. The cell population is a mixture of a series of cells in a proliferative, quiescent, and already differentiated state, and in rapidly proliferating tissues, its growth index can approach 100%. Resting, non-cell cycle cells are poorly susceptible to injury, as cytotoxic drugs are highly lethal to rapidly growing cell populations; hormonal drugs inhibit cell growth, so the combined application of the two is theoretically implausible. Another manifestation of spatial individualization is the difference in the distribution of common tumors in different geographical areas and different human races, and also in the difference in the age of tumor onset. Therefore, the tumor treatment strategy and prognosis of treatment are inevitably influenced by spatial individualization.
②Individualization of anatomical distribution and morphological histology; there are certain differences in the development and regression of breast cancer depending on the site of its occurrence and the site of its metastatic cancer. There is a significant difference between the prognosis of non-specific breast cancer (common) and specific types of breast cancer (less common, such as mucinous adenocarcinoma, etc.), and such and such differences are one of the factors that must be considered when developing treatment strategies.
(3) Individualization at the molecular level (or genetic level): The individualization of biomarkers, genotypes and gene protein expression of tumor patients is manifested in the whole process of tumor development, and there are corresponding changes in biomarkers, genotypes and gene protein expression (polymorphism) in the same type of tumor patients, different clinical periods and therapeutic interventions of the same patients; and the same biomarkers, genotypes and gene proteins can be expressed in different tumors. The same biomarkers, genotypes and gene proteins can be expressed in different tumors.
Due to the “polymorphism” of gene expression in individual patients or corresponding tumors, theoretically speaking, if drugs and their doses can be selected according to gene expression in different patients with the same disease, it should be the basic guarantee for the best therapeutic effect. For example, due to the polymorphism of methyltransferase gene in different patients, the dose of 5-FU needs to be adjusted significantly; capecitabine (Siroda) can only work maximally in tumors that overexpress thymidine nucleoside phosphorylase (the remission rate for third-line treatment of metastatic breast cancer is about 12%, and is expected to reach 25%-50% if screening is performed).
Differences in the prognosis of patients with the same tumor are associated with differences in the molecular biology of the tumor presentation, and unfortunately, despite the considerable amount of research that has been and continues to be devoted to this area, the prediction of these factors (for the most part) on tumor prognosis is still in the exploratory stage and clinical guidance is poor. There are limited molecular biology indicators that have definite clinical guidance, but ER, PR and c-erbB-2 are definitely useful for treatment guidance, but the standardization and quality control of the tests are still influenced by many subjective and objective factors. Therefore, individualized treatment based on molecular biology theory is still only a dream (consensus of the 3rd EORTC/NCI International Conference on Molecular Markers of Tumors).
The main manifestation of non-standardized treatment is the confusion in the design of comprehensive treatment (treatment strategy) and the unreasonable primary treatment; the second manifestation is the arbitrariness of surgery, radiotherapy and chemotherapy, i.e. the lack of standardized concept.
⑤ Individualization of socio-psychological factors: It can be unapologetically said that the socio-economic status, i.e., the patients’ financial ability, is different from the current medical level of cancer treatment, and there are obvious differences in the survival time and quality of survival of patients with the same stage of cancer. This is a sociological problem that cannot be well solved at present. Psycho-psychological factors have a definite correlation with the development of tumor and treatment outcome, however, psycho-psychological factors are prognostic factors without clear metrics, which are difficult to grasp in the process of clinical practice. Therefore, when dealing with a specific patient, it is necessary for the clinician to think deeply about the following issues before making an effective medical plan.
The tension between humanitarian and social benefits;
The tension between survival and quality of life;
The contradiction between the care of the patient and the impact on the future life of relatives.
4. The end goal of clinical practice
Medicine is ultimately an empirical science, and even the current widely advocated “evidence-based medicine” is derived from empirical science (Figure 37-6). When applying the results of large randomized controlled trials (RCTs), clinicians should change the habit of “listening to foreign information” and “pandering to foreigners” and use their own experience to add their own rationalized thinking and judgment to determine the applicability of such evidence to individuals in specific situations. The RCT is a good way to determine whether the evidence is applicable to the individual in a particular situation. At the same time, when analyzing the findings of RCTs, it is important to analyze.
(i) the comprehensiveness of the primary data collected by the researcher;
(ii) whether the strategy and information sources, selection of observation time, and inclusion and exclusion criteria were the same;
③Whether the evaluation indicators of each study were endpoint indicators or intermediate indicators;
④In addition to effectiveness, whether the studies reported indicators such as adverse effects, lost to follow-up and cost-benefit ratio, and whether they were compared accordingly.
In summary, the principles of individual patient treatment planning should be based on evidence-based medical results and empirical medical information, and the concept of “human-centeredness” should be demonstrated to provide the best individualized treatment plan for patients.
II. Clinical practice strategy
1.Surgical treatment
In the past 30 years, among the local-regional treatment modalities for operable breast cancer, the scope of surgery has been significantly reduced, and breast-conserving treatment has become one of the standard treatment modalities for operable breast cancer. There is a wide range of evidence-based medical data on breast-cancer-preserving treatment studies, and the most representative randomized group studies are mainly the prospective studies of the National Cancer Institute of Milan, the NSABP, the European Research and Treatment of Cancer Collaborative Group (EORTC), and the DBCG-82T in Denmark.
The findings were consistent across study groups, with no statistically significant differences in tumor-free survival (DFS) or recurrence-free survival (RFS) and overall survival (OS) between the two groups when comparing breast-preserving treatment with radical mastectomy. Sentinel lymph node biopsy (SLNB) for breast cancer is one of the current hot issues in breast cancer surgical treatment research, and SLNB provides a new idea to further narrow the scope of surgical treatment for breast cancer.
Selection of local treatment procedure Breast-preserving surgery as an alternative to radical mastectomy must meet the following basic guidelines.
(i) Supported by the patient’s evaluation of breast preservation requirements and quality of life (QOL) expectations;
(ii) Theoretical support for obtaining the same survival rate as radical mastectomy;
(iii) technical support to ensure that the postoperative recurrence rate is similar to that of radical mastectomy;
(iv) there is clinicopathological support to make the preserved breast have certain aesthetic effect. Specific factors that influence the choice of local-regional treatment modality for operable breast cancer include the aesthetic outcome after treatment, the risk of local recurrence, and the patient’s attitude toward breast preservation. The following factors need to be considered for specific selection.