Knowing Cancer Diagnosis is a Protective Factor for the Survival of Patients With Breast Cancer : A Retrospective Cohort Study

Background: The health burden of breast cancer is rising in China. The effect of informed diagnosis on long-term survival has not been fully understood. This retrospective cohort study aims at exploring the association between early informed diagnosis and survival time in breast cancer patients. Methods: 12,327 breast cancer patients were enrolled between October 2002 and December 2016. Potential factors including knowing cancer diagnosis status, gender, age, clinical-stage, surgical history, the grade of reporting hospital and diagnostic year were registered. We followed up all participants every 6 months until June 2017. Results: By June 2017, 18.04% of the participants died of breast cancer. Both the 3-year and 5-year survival rate of whom knew cancer diagnosis were longer (P<0.001). By stratied analysis, except subgroups of male patients and patients in stage III, patients knowing diagnosis showed a better prognosis in all the other subgroups (P<0.05). By Cox regression analysis, it was showed that not knowing cancer diagnosis was an independent risk factor for survival in breast cancer patients (P<0.001). Conclusions: Being aware of their cancer diagnosis plays a protective role in extending the survival time in breast cancer patients, which suggests medical staff and patients’ families disclose cancer diagnosis to patients timely.

have affected breast cancer risk by reducing the lifetime duration of breastfeeding [8]. Obesity and low levels of physical activity are both known as risk factors for breast cancer in western countries. With the rapid growth of nance in China, these may also play as a risk factor for breast cancer in China [11].
Other factors such as height, hormone replacement therapy, and family history have also been regarded as risk factors of breast cancer for Chinese women [11,12]. However, few studies paid attention to psychological factors such as the association between cancer diagnosis disclosure and survival time of patients with breast cancer.
People display different attitudes towards life with their age grows. Some studies found that patients of different ages may display different emotional experience. Although the incidence of breast cancer is increased with the growth of age, younger patients may be the most likely to suffer emotional distress compared to older ones. This relationship can be observed in patients ranging from 30 to over 80 years old [13,14]. Also, there was another study claimed a non-signi cant correlation between age and affective distress by examining the above association 10 months after diagnosis [15]. However, unrealistic optimism may be more prevalent among older patients [16]. Most studies had a limited sample size, which may affect the effectiveness of the conclusions.
It has traditionally been a controversial topic that whether or not to fully inform patients of their cancer diagnosis. Advocates of concealing the condition to patients argue that patients who know their cancer diagnosis are liable to experience signi cant distress, which may lead to a worse prognosis [17]. Studies in Iran and Turkey showed that patients knowing their diagnosis were more likely to undergo depression, psychiatric morbidity and other negative emotion [18,19]. On the other hand, patients who lack the awareness of their condition may undergo unrealistic optimism, which may lead to unfavorable behaviors and nally result in adverse health outcomes [20]. Previous researches showed that having an appropriate perspective of cancer status improved patients' participation in the treatment, as well as reduced their distress level, which helped them meet their psychological needs with self-esteem and respect [21]. On the contrary, without knowing their cancer condition results in an uncompleted understanding of their diagnosis, which would hurt the trust relationship between patients and physicians [22]. Depending on a study of a total of 127 cancer patients and their caregivers, no signi cant difference was found before and after disclosing the cancer diagnosis to patients, while the quality of life could be improved with psychological care intervention [23].We have found that knowing their cancer status would carry a better survival rate in patients with lung cancer, while there were few studies about this issue in breast cancer patients [24].
The association between diagnosis disclosure of breast cancer and the prognosis of patients was detected in this retrospective cohort study based on the baseline and long-term follow-up information of a large sample. The results may provide valuable evidence for clinical practice.

Methods
The study was designed to nd out the role that knowing cancer diagnosis plays in the survival rate of patients with breast cancer by collecting information of patients with different backgrounds. Community doctors followed up patients by telephone or household survey every 6 months, and regarding death as the primary outcome event. The follow-up ended in June 2017.
Statistical analysis χ 2 tests are used to explore all categorical variables. One-way analysis of variance (ANOVA) was conducted to compare continuous variables. Life table was used to calculate the 3-year survival rate and 5-year survival rate, and to compare the differences between subgroups in survival curve. The Cox proportional hazard regression model (Forward Stepwise, Likelihood Ratio test) with hazard ratios (HR) and 95% con dence intervals (CI) calculated was used to conduct multivariate analysis of factors in uencing survival time. Statistical Package for Social Sciences software (version 23.0, SPSS, Inc., Chicago, IL) was used to conduct all statistical analyses which were two-sided. P < 0.05 was de ned as statistically signi cant.

Baseline characteristics
A total of 12327 patients with breast cancer were enrolled in this study. Table 1 shows the baseline characteristics of the participants. Among all 12327 participants, 9466 (76.79%) patients were aware of their cancer, 2756 (22.36%) patients had no idea of their situation. There were 105 (0.85%) patients' knowledge of their diagnosis was unclear. As shown in Table 1, there was no difference in gender composition between participants who knew their diagnosis and those who didn't know (women accounted for 99.26% vs. 99.24%, P = 0.904). Signi cant differences could be found in age, clinical stage, surgical history and reporting hospital-grade between patients who knew their diagnosis and those who didn't know (P < 0.05). A trend of telling patients of their cancer diagnosis was found also by noticing the difference between different phases of diagnostic time (when participants were diagnosed with breast cancer, 1: before 2006, 2: 2007-2011, 3: 2012-2016, Linear-by-Linear Association: value = 4.232, P = 0.040). Patients who knew their diagnosis had younger average age (55.97 ± 11.94 vs. 60.49 ± 14.20, P < 0.001), earlier clinical stage (stage 0-I: 31.94% vs. 22.28%, P < 0.001), higher surgery rate (56.20% vs. 49.24%, P < 0.001), and more recent diagnostic year (being diagnosed from 2012 to 2017:40.78% vs. 40.50%, P = 0.001). Besides, patients registered and reported in higher grade hospitals were more likely to be informed of their diagnosis (high-grade hospital: 57.91% vs. 55.70%, P < 0.05). respectively. As shown in Table 2, participants with different characteristics had signi cant differences in prognosis. The 3-year survival rate and 5-year survival rate of patients who knew their diagnosis were both longer than those who didn't know (0.89 vs. 0.79, 0.85 vs. 0.73, P < 0.001). Besides, it was found that female (P = 0.011), younger age (< 35:P < 0.001), earlier clinical stage (P < 0.001), higher rate of surgery (P < 0.001), being diagnosed more recently (P < 0.001) and reported from higher grade hospitals (P < 0.001) contributed to better survival rate. Strati ed analysis of the impact of cancer diagnosis knowledge on survival time in patients with breast cancer As shown in Table 3, participants were strati ed by gender, age, clinical stage, surgery history, diagnostic time and grade of reporting hospital to explore the relationship between awareness of cancer diagnosis and prognosis. Except in male patients(P = 0.103) and in the subgroup of patients in stage Ш (P = 0.265), patients who knew their cancer diagnosis displayed a better survival rate than those who didn't know (P < 0.05).  Table 4). In addition, compared to patients in Stage 0-I, the more advanced stage patients in, the poorer prognosis they would have (HR,2.085, 4.988, and 13.953, respectively; P < 0.001, Table 4).

Discussion
According to our long-term follow-up research of a large size sample, disclosure of patients' diagnosis was found to be a protective factor for the longer survival time of patients with breast cancer through univariate and multivariate analyses. Age, clinical-stage, surgical history and diagnosis year were also associated with patients' survival time.
The disclosure of cancer diagnosis to patients with breast cancer has always been a contentious topic all over the world. Owing to the different cultural backgrounds of different countries, opinions on this topic are varied. There was a survey indicated that in the United Kingdom, almost all patients wanted to be aware of their diagnosis while in Asian culture, physicians and family members may worry more about whether to inform [25]. What's more, there is a change of attitude when the hypothetic diagnosis changed from the initial stage to the terminal stage. The percentage of those who wanted to reveal the diagnosis to patients decrease signi cantly (from 87.5%-40.5%) [26]. The reasons for physicians and family members hesitating to disclose the real to patients may include psychological impact and pain of treatment needed to undergo, especially the loss of physical integrity. It has been proved that losing a breast by mastectomy could bring about severe mental impairments resulted from body image, female identity, self-worth, social interactions and so on [27].
In this study, we found that the popularization of making patients know the diagnosis is increasing year by year, and the disclosure of patients' diagnosis is an independent protective factor for patients with breast cancer to prolong their survival time. Patients without knowing their real condition may form unrealistic optimism which may lead to an unhealthy lifestyle making their condition worse. In contrast, having a clear perspective of their cancer status will lead to a healthier way of life. Informing patients of their breast cancer as early as possible assists them to have a precise knowledge of themselves. What's more, there are many strategies to help patients cope with their emotional distress such as psychological care and breast reconstruction, which have had some effectiveness already [28,29].
In male patients' subgroup, diagnosis disclosure was not linked with survival time. Male breast cancer is uncommon, and there were only 93(0.75%) male patients involved in our study. Similarly, there were 2470 (0.98%) men with breast cancer in the USA while 252,710 women with breast cancer in 2017 [30]. Since most data for breast cancer research are from female patients, men tend to be diagnosed with breast cancer at a later age than women since most treatment and diagnostic decisions are made by female patients' data [31]. In addition, breast cancer appeared in female patients more frequently, therefore, male patients may undergo a special perceptual experience. Because of the gender stereotype, male patients knowing their diagnosis were more likely to have a high level of cancer-speci c distress and depressive symptoms [32]. More researches may be needed on the psychological state of this particular and rare group.
Our study found that disclosure of cancer status and other factors such as female, younger age, earlier clinical stage, surgical history, and more recent diagnostic year were signi cantly related to better survival. The more recent diagnostic year predicts a shorter time for cancer to develop and more advanced treatment to receive. In addition, there were more patients being told of their own cancer status in which group was diagnosed currently. Therefore, patients with these conditions may have a better prognosis.
In our study, we use a narrow de nition of cancer disclosure, only focusing on informing patients of their cancer diagnosis, but not considering the patient's knowledge of treatment, prognosis, and other relevant information. We didn't obtain detailed information about the treatment that participants were received, which may in uence the nal result of participants. Because of challenges in data collection and uncertainty, some potential factors such as psychological condition of patients, education level and income were not included. In the following research, patients might be concerned about their own conditions, however, the decision patients' families made at the rst time may re ect patients' characteristics to some extent. So we regarded their diagnosis were concealed if they didn't know their own condition when they were enrolled in our study. Despite the above limitations, this retrospective cohort study provides clear evidence to promote the diagnosis disclosure to breast cancer patients through long-term follow-up of a large sample size, which hopefully offer a new direction in clinical practice.
Our study offered consequences that more and more medical staff and patients' families are more and more willing to disclose the truth to patients according to our analysis on diagnostic year, which implies that knowing cancer status predicts a better prognosis and longer survival time than those who don't know. It is positive evidence suggests that disclosing the diagnosis to patients does better to patients' survival with breast cancer. Previous studies showed that most patients were ready to have su cient knowledge of their diagnosis while the majority of medical staff and families were not [33]. The reason for this phenomenon may be that it is a di cult task of revealing cancer diagnosis to patients, which would make physicians feel uncomfortable and unprepared [34,35]. With the consent right becomes ever more common, the debate between whether to tell patients their diagnosis would be replaced by how and when to tell. Existing guidelines for breaking bad news based on expert opinion are available [36].
However, some guidelines were found not completely derived from empirical data [37]. Therefore, formal guideline for breaking bad news is necessary to be made. Furthermore, oncological care for patients is also needed to help them keep a positive attitude towards their cancer status and overcome their emotional distress [38].

Conclusions
Based on the long-term follow-up of a large sample, the popularization of disclosure of cancer diagnosis to patients has increased as time go on which may contribute to a longer survival time in patients with breast cancer. Even though it may arouse emotional distress in patients after being told of their cancer status, with more adequate information on their condition and better skills of medical staff to disclose it, patents would bene t from it in the long-term. Our nding provides further evidence to disclose cancer diagnosis to patients. Formal guidelines of medical staff to reveal cancer diagnosis and education for patients' families of psychological care need further complement in clinical practice.

Declarations
Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later comparable ethical standards. The study was approved by the Bioethics Committee of Second Military Medical University.

Consent for publication
Written informed consent for publication of their clinical details was obtained from the patient/parent/guardian/ relative of the patient. A copy of the consent form is available for review by the Editor of this journal.

Availability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests. Author's contributions TS and XPL conceived and designed the study. CH, Wen Xi Zhu, YXT, YHB, ZL and XPL collected the data.
CH, JFX and TS analyzed the data. The rst draft of the manuscript was written by CH. HW, SYX, JZX, LX, RKZ, YJW, JD and YJH commented on designation and modi cation of the manuscript. All authors read and approved the nal manuscript.