Associated Morbidity in Screened and Diagnosed Breast Cancer Patients: A Retrospective Study

Diane B-I; Birgit C; Serge R

Research Article

Austin J Obstet Gynecol. 2021; 8(6): 1187.

Associated Morbidity in Screened and Diagnosed Breast Cancer Patients: A Retrospective Study

Diane B-I, Birgit C and Serge R*

Department of Obstetrics and Gynecology, Isala Breast Unit and Prevention Centre, University Hospital Saint-Pierre (Université Libre de Bruxelles and Vrije Universiteit Brussel), Brussels, Belgium

*Corresponding author: Serge Rozenberg, Department of Obstetrics and Gynecology, Isala Breast Unit and Prevention Centre, University Hospital Saint-Pierre (Université Libre de Bruxelles and Vrije Universiteit Brussel), Brussels, Belgium

Received: June 25, 2021; Accepted: July 09, 2021; Published: July 16, 2021

Abstract

Introduction: Breast Cancer (BC) screening has been associated with reduced mortality and morbidity. This study compares tumor characteristics and treatment morbidity in screened versus diagnosed women.

Materials and Methods: This retrospective study, conducted between 2010 and 2013, included 666 BC screened or diagnosed patients. We compared patients and tumors characteristics and received treatments. We also analyzed the results after excluding patients at risk of BC and conducted a multivariate analysis to assess odds ratios (OR).

Results: Screened women had smaller tumors (16.5 vs. 22.6 mm, p<0.001), of lower grade (p<0.001) with a lower Proliferation Index (PI) (p<0.001) than diagnosed women. Screened women were more frequently treated using conservative surgery (82.8% vs. 59.7%, p<0.001), needed less often axillary dissection (15.1% vs. 35.4%, p<0.001) and less often chemotherapy (20.8% vs. 48.3% p<0.001) than diagnosed women. In the multivariate analysis after adjustment for age and BC history, diagnosed women had increased (OR: 4.79, 95% IC: 3.19-7.18) risk to be administered chemotherapy and to undergo axillary dissection (OR: 4.18, 95% IC: 1.56-11.17) than screened women.

Conclusion: Patients should be informed about the benefits in terms of morbidity that screening confers to them.

Keywords: Breast cancer; Screening; Morbidity; Treatments

Introduction

While Breast Cancer (BC) remains the most frequent cancer in women, its mortality decreased in most high-income countries during the last decade [1]. This is generally attributed to treatment improvement and screening, resulting in earlier diagnosis and better prognosis, although the latter has been highly debated [2,3]. Indeed, while some studies estimated that organized screening contributes to a twenty percent reduction in BC mortality [4,5], others challenged these data and reported increased harm due to a 30-50 % BC overdiagnosis resulting from screening [6].

Both “true BC” and “over-diagnosed cancer” may be associated with considerable physical and psychological morbidity [7,8]. Nevertheless, screening is supposed to improve quality of life due to the early stage of the cancer and the associated less aggressive treatment than in symptomatically diagnosed cancers. This may theoretically be true, but has not often be studied [9]. In this retrospective analysis, we quantify the morbidity due to BC and its treatments in “Screened Women” (SW) as compared to that of symptomatic women, defined as “Clinically Diagnosed Women” (CDW). We further quantified the BC morbidity in diagnosed and screened women, after having excluded women at risk of breast cancer due to a family history.

Materials and Methods

Study design: retrospective cohort study

Patients selection: We analyzed systematically all the data of patients diagnosed with BC from January 2010 and December 2013 (n=669) in the C.H.U Saint-Pierre, a community and university hospital situated downtown Brussels, and treating a multicultural population.

Screened tumors were discovered by mammography in asymptomatic women who were invited to be screened by the Brussels region (“Mammotest program”) or were send by their physician for opportunistic screening. The uptake of organized screening is rather low in Brussels, (and this is in part due to the complex administrative bilingual situation of the Brussels district). That is why many women are still send by their physicians for opportunistic screening every two years (as for organized screening) or every year when they have a first-degree family history of breast cancer.

Screened women under 50 and over 69 years-old had opportunistic screening given the fact that organized screening does not apply to them, although more and more physicians and opinion leaders consider that there is a place for screening at those ages.

Clinically diagnosed tumors included symptoms such as feeling a mass, an axillary adenopathy, mammary discharge, pain, skin retraction, ulceration, pleural effusion or symptoms related to a metastasis. We excluded male patients and those fortuitously discovered (during breast reduction) (n=3).

We collected data about the date of BC detection, mode of detection and tumors characteristics. These data were collected systematically and are forwarded to the Belgian Cancer registry.

Tumors’ characteristics

We included stage, size, whether there was extensive disease (node and metastasis), the Elston-Ellis histopronostic grade (ranging from I to III), whether the tumor was in situ or invasive, lobular or ductal, the expression of estrogen and progesterone receptors, the proliferation index (classified as low when the Ki67<15% and high when Ki67>15%) and the presence of HER2 gene amplification.

Treatment characteristics: The following information about treatment was collected: type of surgery (lumpectomy, mastectomy, axillary lymph node dissection, removal of the sentinel node), radiotherapy, neo-adjuvant chemotherapy or chemotherapy postsurgery, use of hormone-therapy and immunotherapy.

Outcomes: In particular, we considered as surrogate markers of morbidity: having a mastectomy versus a lumpectomy, an axillary Lymph Node Dissection (LND) versus the removal of the sentinel node and undergoing chemotherapy or not.

Power analysis

We calculated that using a power of 80% (type II error) and type I error of 5% and hypothesizing a 50% reduction of needed chemotherapy (p (diagnosed) = 0.50 vs. p(screened)= 0.25; n=55), of mastectomy (p (diagnosed) = 0.4 vs. p(screened) =0.2, n=79) less than 100 patients were needed.

Statistical analyses

Groups were compared using Chi-squared test, Fisher’s exact test for small numbers and t tests. The first analysis compared tumors’ characteristics and treatments between all screened and clinically diagnosed women (Table 1). Characteristics were expressed in mean + standard deviation or median (IQR) when there were continuous and in percentage when they were categorical. In order to reduce the risk of bias, we conducted a second analysis, excluding women with relevant BC risk factors (such as personal and/or 1^st, 2^nd or 3^rd degree family BC history, or genetic BC predisposition) and stratified these analyses by age classes (40-49, 50-69 and 70-75 years old) (Figure 1).

Table 1: Characteristics of screened and diagnosed tumors before excluding at risk patients (Global analysis).




  
    Characteristics 
    Screened Tumors (n= 279) 
    Clinically Diagnosed Tumors    (n= 387) 
    p
  
  
    Women’s    Characteristics 
    
    
    
  
  
    Mean age (years-old) [SD]
    57 [11] 
    59 [15] 
    0.196 
  
  
    % with personal and/or familial BC history
    34.6 
    37.7 
    0.436 
  
  
    Tumors’    Characteristics 
    
    
    
  
  
    Mean size (mm) [SD] 
    16,46 [15,40] 
    22,62 [19,27] 
    <0.001 
  
  
    Median size (mm) [IQR] 
    12 [9] 
    17 [13] 
    
  
  
    Grade (%): 
    
    
    
  
  
    
      1 
    
    25.4 
    16 
    
  
  
    
      2 
    
    45.9 
    45.7 
    0.001 
  
  
    
      3 
    
    19.7 
    29.7 
    
  
  
    % invasive carcinoma 
    74.2 
    87.4 
    <0.001 
  
  
    % in situ carcinoma 
    18.3 
    7.2 
    <0.001 
  
  
    % ductal carcinoma 
    79.9 
    83.5 
    0.48 
  
  
    % lobular carcinoma 
    18,3 
    15,0 
    
  
  
    % node positive 
    5.7 
    19.7 
    <0.001 
  
  
    % ER positive 
    79.9 
    71.8 
    0.017 
  
  
    % PR positive 
    74.2 
    66.9 
    0.043 
  
  
    Ki 67 >15% 
    13.6 
    28.7 
    <0.001 
  
  
    HER2 gene amplification    (%) 
    4.7 
    12.1 
    0.005 
  
  
    Metastasis (%) 
    2.9 
    14 
    <0.001 
  
  
    Treatments’    Characteristics 
    
    
    
  
  
    Lumpectomies (%) 
    82.8 
    59.7 
    <0.001 
  
  
    Mastectomies (%) 
    15.8 
    29.5 
    <0.001 
  
  
    Removal sentinel node (%) 
    75.6 
    44.7 
    <0.001 
  
  
    Axillary LND (%) 
    15.1 
    35.4 
    <0.001 
  
  
    Chemotherapy (%) 
    20.8 
    48.3 
    <0.001 
  
  
    Hormonotherapy (%) 
    77.1 
    62.5 
    <0.001 
  
  
    Radiotherapy (%) 
    83.5 
    74.9 
    0.008 
  
  
    SNL: Sentinel Node; LND: Lymph Node.



Table 1: Characteristics of screened and diagnosed tumors before excluding at risk patients (Global analysis).

Figure 1: Flow chart of the patients’ selection: Patients were divided in 3 groups according to their age. In a second analysis, we excluded patients with a family or personal BC history.

    
    
    Figure 1: Flow chart of the patients’ selection: Patients were divided in 3 groups according to their age. In a second analysis, we excluded patients with a family
or personal BC history.

A multivariate analysis was also conducted to examine the effect of the screening versus clinical diagnosis on having a mastectomy versus a lumpectomy, an axillary Lymph Node Dissection (LND) versus the removal of the sentinel node and undergoing chemotherapy or not. A p-value ≤0.05 was considered as statistically significant. All analyses were conducted using SPSS 25.

The study was approved par the local ethical committee (N° O.M.007).

Results

Characteristics of patients, tumors and received treatments (Global analysis of screened versus diagnosed patients Table 1).

From January 2010 to December 2013, 666 BC have been diagnosed in patients aged 21 to 96 years old. More than a third of them had a personal or family BC history.

Screened patients who had BC, had tumors that were less aggressive than BC patients diagnosed for symptomatic tumors. For instance, screened women had tumors of lower grade (p<0.001), lower stage and had three times less often involved nodes (19.7% vs. 5.7%) (p<0.001) than diagnosed women. Screened women were also more likely to have tumors expressing hormonal receptors and had twice less often tumors overexpressing HER2 receptors (Table 1).

Similarly, screened women had twice less often mastectomies (15.8% vs. 29.5%, p<0.001) and chemotherapy (20.8% vs. 48.3% p<0.001), but more often sentinel node removal (75.6% vs. 44.7%, p<0.001), radiotherapy and hormone-therapy than diagnosed women (Table 1).

Characteristics of tumors and treatments after exclusion of women with a personal or familial history of BC, stratified by age (Figure 1, Table 2).

Table 2: Characteristics of screened and diagnosed tumors in patients without familial or personal BC history, stratified by age and by mode of presentation.




  
    Characteristics 
    40-49 Years-Old 
    50-69 Years-Old 
    70-75 Years-Old 
  
  
    
    Screened    tumors (n=37) 
    Clinically    diagnosed tumors (n=38) 
    p
    Screened    tumors (n=104) 
    Clinically    diagnosed tumors (n=98) 
    p
    Screened    tumors (n=15) 
    Clinically    diagnosed tumors (n=27) 
    p
  
  
    Stage T    (%) 
    
    
     
    
    
     
    
    
     
  
  
    Tis 
    23.3 
    7.2 
    <0.001 
    18.9 
    5.6 
    <0.001 
    0 
    10.6 
    <0.001 
  
  
    T1a-T1b 
    33.3 
    14.5 
    // 
    33.7 
    16.8 
    // 
    63 
    12.8 
    // 
  
  
    T1c 
    28.3 
    30.4 
    // 
    29.6 
    31.8 
    // 
    22.2 
    29.8 
    // 
  
  
    T2 
    8.3 
    37.7 
    // 
    7.1 
    24 
    // 
    7.4 
    31.9 
    // 
  
  
    T3 
    1.7 
    4.3 
    // 
    0.6 
    7.3 
    // 
    0 
    6.4 
    // 
  
  
    T4 
    0 
    4.3 
    // 
    0.6 
    6.1 
    // 
    3.7 
    6.4 
    // 
  
  
    Stage    N (%) 
    
    
     
    
    
     
    
    
     
  
  
    N0 
    83.3 
    72.5 
    0.029 
    76.3 
    68.7 
    0.036 
    81.5 
    68.1 
    0.359 
  
  
    N1 
    1.7 
    15.9 
    // 
    6.5 
    16.2 
    // 
    7.4 
    19.1 
    // 
  
  
    N2 
    0 
    0 
    // 
    0 
    0.6 
    // 
    0 
    0 
    // 
  
  
    N3 
    0 
    1.4 
    // 
    0 
    0.6 
    // 
    0 
    0 
    // 
  
  
    Stage    M (%) 
    
    
    
    
    
    
    
    
    
  
  
    M1 
    0 
    10.1 
    0.04 
    0 
    3.9 
    0.027 
    3.7 
    12.8 
    0.436 
  
  
    Other Tumors’    Characteristics 
    
    
    
    
    
    
    
    
    
  
  
    Mean size (mm) 
    18.34 
    18.05 
    0.703 
    16.27 
    22.76 
    0.001 
    9,87 
    25,42 
    0,002 
  
  
    [SD] 
    [15.29] 
    [14.22] 
     
    [16.13] 
    [18.21] 
     
    [5,64] 
    [17,75] 
     
  
  
    % ductal tumors 
    91.7 
    81.6 
    0,205 
    77.9 
    83.7 
    0,298 
    73.3 
    77.8 
    0,746 
  
  
    % lobular tumors 
    8.3 
    15.8 
    0,327 
    20.2 
    14.3 
    0,268 
    26.7 
    22.2 
    0,746 
  
  
    % ER positive 
    80 
    72.5 
    0.158 
    79.3 
    72.6 
    0.146 
    85.2 
    66 
    0.073 
  
  
    % PR positive 
    73.3 
    65.2 
    0.209 
    75.7 
    67 
    0.073 
    74.1 
    63.8 
    0.365 
  
  
    % with Ki 67 >15%
    15 
    30.4 
    0.012 
    13.6 
    26.8 
    0.022 
    7.4 
    29.8 
    0.02 
  
  
    HER2 gene amplification (%) 
    3.3 
    14.5 
    0.003 
    4.1 
    11.7 
    <0.001 
    11.1 
    2.1 
    0.078 
  
  
    Grade (%): 
     
     
     
     
     
     
     
     
     
  
  
    
      1 
    
    32.4 
    21.1 
    
    26.9 
    15.3 
    
    26.7 
    25.9 
    
  
  
    
      2 
    
    40.5 
    36.8 
    0.363 
    45.2 
    51 
    0.038 
    60 
    37 
    0.302 
  
  
    
      3 
    
    21.6 
    34.2 
    
    14.4 
    25.5 
    
    6.7 
    22.2 
    
  
  
    Metastasis (%) 
    1.7 
    14.5 
    0.009 
    3 
    12.3 
    0.003 
    0 
    17 
    0.023 
  
  
    Treatments’    Characteristics 
    
    
    
    
    
    
    
    
    
  
  
    Lumpectomies (%) 
    85.0 
    72.5 
    0.085 
    81.7 
    63.1 
    <0.001 
    92.6 
    57.4 
    0.001 
  
  
    Mastectomies (%) 
    13.3 
    23.2 
    0.151 
    17.8 
    32.4 
    0.002 
    7.4 
    25.5 
    0.055 
  
  
    Removal SNL node (%) 
    75 
    47.8 
    0.002 
    75.1 
    48.3 
    <0.001 
    81.5 
    52.2 
    0.012 
  
  
    Axillary LND (%) 
    13.3 
    42 
    <0.001 
    16 
    38.8 
    <0.001 
    11.1 
    17.4 
    0.469 
  
  
    Chemotherapy (%) 
    31.6 
    65.2 
    <0.001 
    18.3 
    49.7 
    <0.001 
    18.5 
    27.7 
    0.378 
  
  
    Hormonetherapy (%) 
    76.7 
    53.6 
    0.016 
    79.3 
    65.9 
    0.005 
    77.8 
    57.4 
    0.078 
  
  
    Radiotherapy (%) 
    86.7 
    84.1 
    0.677 
    82.2 
    82.1 
    0.976 
    88.9 
    59.6 
    0.008 
  
  
    SNL: Sentinel Node; LND: Lymph Node.



Table 2: Characteristics of screened and diagnosed tumors in patients without familial or personal BC history, stratified by age and by mode of presentation.

Table 3: Likelihood of received treatments, according to the mode of BC detection (screened or clinically diagnosed): Binary logistic regression.




  
    Age    Groups 
    Lumpectomy vs. Mastectomy 
    SNL Node Removal vs. Axillary LND
    Chemotherapy vs. No Chemotherapy 
  
  
    p
    OR (IC    95%) 
    p
    OR (IC    95%) 
    p
    OR (IC    95%) 
  
  
    All 
    <0.001 
    2.61 (1.72-3.95) 
    <0.001 
    4.46 (2.88-6.91) 
    <0.001 
    4.79 (3.19-7,18) 
  
  
    40-49 y-o 
    0.454 
    
    0.004 
    4.18 (1.56-11.17) 
    <0.001 
    4.47 (1.97-10.15) 
  
  
    50-69 y-o 
    0.002 
    2.63 (1.53-4.54) 
    <0.001 
    4.64 (2.62-8.21) 
    <0.001 
    5.27 (3.07-9.04) 
  
  
    70-75 y-o 
    0.132 
    
    0.085 
    
    0.148 
    
  
  
    SNL: Sentinel Node; LND: Lymph Node.



Table 3: Likelihood of received treatments, according to the mode of BC detection (screened or clinically diagnosed): Binary logistic regression.

After stratification by age (in the three studied age groups) and exclusion of women with a personal or family BC history, similar results were observed than in the global analysis. Screened patients of all ages had tumors that were less advances and had lower proliferation indices than diagnosed women (Table 2). Screened women aged 40-49 and 50-69 had three times more often in situ tumors, less often-invaded nodes and less often HER2 gene overexpression than diagnosed women (Table 2). Screened women aged 50-69 and 70-75 had smaller tumors than diagnosed women (p<0.001 and p<0.002). After stratification, no significant difference between groups was observed concerning expression of hormonal receptors.

Similarly, screened women, regardless of age, had more often sentinel node removal. Screened women aged 50 -69 were more often treated by lumpectomy (81.7% versus 63.1% (p<0.001) and less often by mastectomy (17.8% versus 32.4%) than diagnosed women. Diagnosed women aged from 40-49 and 50-69 years old were treated more often using chemotherapy than screened women (respectively 65.2% vs. 31.6% and 49.7% vs. 18.3%, p<0.001).

Multivariate analysis

Using a multivariate analysis, after adjustment for age and BC history, diagnosed BC patients were twice more likely to be treated by mastectomy than by lumpectomy (OR: 2.61, 95% IC: 1.72-3.95), four times more likely to have an axillary lymph node dissection rather than a sentinel node removal (OR: 4.46, 95% IC: 2.88-6.91) and five times more like to be treated by chemotherapy (OR: 4.79, 95% IC: 3.19-7.18) as compared to screened women.

On the other hand, no significant differences were observed concerning treatments between screened and clinically diagnosed women, who were older than 70 years of age.

Discussion

The advantages and risks of BC screening have been much debated [2,4,9]

In brief, the optimal way to compare mortality and morbidity in screened and unscreened groups requires randomized trials with large uptakes and a long follow-up. Nevertheless, technology evolves with time, which means that long-term evaluation of imaging technics in term of accuracy, precision or irradiation is difficult since these will have improved in the meantime.

Most randomized trials and meta-analysis of these trials with long follow-up estimated that screening provides a 20% reduction in breast cancer mortality. Nevertheless, several uncertainties exist [10]. The major recognized harm of screening is overdiagnosis, i.e., a cancer that has been discovered by screening, but that would not otherwise have come to attention in the woman’s lifetime. Even more, uncertainties exist about the magnitude of over-diagnosis than about the mortality reduction, but many experts have estimated the risk of overdiagnosis to be in the range of 10-20 % [10].

The subject is therefore complex, and this study does not have the ambition to provide an answer to that question. Nevertheless, we aimed to analyze in our daily practice the tumor and treatment characteristics of screened patients versus symptomatically diagnosed patients. Our study is different from some others because it provides additional information on patients BC history and, therefore, allows us to assess women at lower risk of BC.

We observed that more than one-third of patients had at least one family and/or personal history of BC. (34.6% among SW and 37.7% among CDW).

After excluding women with a family or personal history of BC, we observed that screened women younger than 50, were more likely to be treated by sentinel node removal and less likely to be administered chemotherapy than symptomatic diagnosed women. On the other hand, there was no difference between both groups regarding the proportion of conservative surgery or the average tumor’s size, contrary to other studies reporting smaller and lower in grade tumors in screened than in clinically diagnosed tumors [11- 14]. It should be noted that, in the age group 40-49 screening is not advocated by most guidelines or the Belgian authorities.

Patients aged from 50-69, who had been screened, as suggested by Belgian guidelines, had more often conservative surgery than women whose tumor had been diagnosed due to symptoms (83% vs. 60%). These figures are higher than those observed by Barth et al. (respectively 56% and 32% of conservative treatments) [9]. Moreover, in our series, screened women had four times more often sentinel node excision instead of axillary node dissection and five times less often chemotherapy than symptomatically diagnosed women. This results in fewer side effects such as arm stiffness, edema, pain and impaired movements, lower risk of neurotoxicity, cardiomyopathy and thromboembolism [15-18].

On the other hand, screened patients older than 70, had not been treated with less aggressive treatments than diagnosed women.

For patients to be able to make an enlightened choice on participating to systematic screening, a clear information needs to be provided. Nowadays, women are informed about the harms of screening such as false positives and over-diagnoses, as well as the risk of false negatives, pain, discomfort, and exposure to increased radiation [19].

Motivation to be screened or not, can result from information about the number of patients needed to be screened (NNS) to prevent one breast cancer death, which, based on a meta-analysis, ranges between 377 for women aged 60-69 years and 1339 for those aged 50- 59 and 1904 for those aged 39-49 years [20]. Knowing that screened cancers are associated with a much-reduced risk of morbid treatment, as compared to diagnosed cancers, may also motivate women to be screened.

The morbidity following treatment of a BC is especially feared for breast surgery, axillary surgery and chemotherapy. In our study, we observed that screened women were between twice and five times more likely to be treated by less harmful treatments than diagnosed women.

Our study is hampered by several limitations: we have not addressed the problem of over-diagnosis in this study, and we cannot rule out that some of the screened tumors with a better prognosis were actually over-diagnosed tumors [21,22]. Unfortunately, currently, in our daily practice, we are unable to distinguish over-diagnosed tumors from tumors that need to be treated [23].

Moreover, we were unable to distinguish women screened opportunistically from those screened through organized screening. We were also unable to assess whether women who had opportunistic screening had had an organized screening in the past or vice versa. The ideal comparison should have been performed between women participating in the organized screening programme, and those who were diagnosed. We were unable to do this, as stated before. This would have result in analyzing even smaller groups, which precludes drawing conclusions. But even in such a setting, differences between screened and unscreened women exist, as it has been observed that screened women are often more aware of their health and use more often menopause hormone therapy [24,25].

Our outcomes included surrogate markers of morbidity: having a mastectomy versus a lumpectomy, an axillary Lymph Node Dissection (LND) versus the removal of the sentinel node and undergoing chemotherapy or not. However, we did not include investigations, such which may also add stress and discomfort, false positive mammography and unnecessary biopsies, false-negative mammography, leading to delayed diagnosis, nor re-operation rates. Women with extremely dense breast tissue have an increased risk of breast cancer, and their cancers are also less likely to be detected on mammography, leading to an increased risk of Interval cancers. This risk may be reduced by supplemental MRI screening [24].

In this study, we were unable to take into consideration this source of bias, as we did not analyze either the mammographic density of screened or diagnosed women.

Conclusion

In conclusion, most expert groups encourage shared decisionmaking with women [27]. In this respect, our study suggest that, although we cannot rule out that screened women had more often over-diagnosed tumors, they underwent more often less aggressive treatments that were associated with less side effects and less morbidity. Patients should be informed about the risk of screening but also the possible associated advantages in terms of morbidity. The current Belgian screening program advertises on its website “being screened reduces the mortality by 20%. Concerning morbidity, there are only a few words: screening is associated with “lighter treatment”. In addition, it does not mention risks associated with screening [28]. The current leaflets mention, however, overdiagnosis risk, and reduced mortality but do not mention possible associated advantages in terms of morbidity associated with screening [29].

Contributors

BC developed the idea of the study. DB collected the data, analyzed them and wrote the first draft. All the authors corrected the manuscript and approved the manuscript.

Conflict of Interest

The manuscript was used in a previous form as a medical student thesis by DB.

References

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Citation: Diane B-I, Birgit C and Serge R. Associated Morbidity in Screened and Diagnosed Breast Cancer Patients: A Retrospective Study. Austin J Obstet Gynecol. 2021; 8(6): 1187.

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