Team:GreatBay SCIE/Human Practices

• Intro
• Understanding the Problem
• Clinical
• Laboratory
• Questionnaire
• Issues with Drug Development
• Aptamers for lower price and specificy
• Nanoparticles for lower side effects and better stability
• Feedback
• Modeling
• Issues Remaining in Society
• Lack of awareness
• Talking with the Chairman
• Further Research with Questionnaire
• Breast and Bra
• Documentary
• Reference

Integrated HP

Intro

Breast Cancer is one of the most prominent cancer presents in females. In 2020, 11.7% of the newly diagnosed cancer cases are breast cancers, the largest among the 36 cancer. Among women, 24.5% of the cancer cases were breast cancer, and 15.5% of death is caused by breast cancer as well^[1]. Stage I breast cancer can be cured with surgical operations; surgeries involve the removal of breast and lymph nodes, in some cases, some chest muscles have to be removed as well. In later stages, chemotherapy and radiotherapy has to be applied as well. However, Chemotherapy and radiotherapy are harmful to the body, causing problems such as falling hair. Targeted drugs remain flawed in many ways, for example, antibody-drug conjugates often cause great side effects; pathway inhibitor drugs rely on specific pathways which sometimes can be bypassed by tumor cells.

Understanding the Problem: Clinical & Laboratory Methods

Clinical

We wish to understand breast cancer not only from statistical perspective, but also from the doctors and the patients; this could help us understand breast cancer in a more practical approach.

Highlights:

To understand how breast cancer is treated clinically, we interviewed doctors who are breasts cancer specialists and also with a breast cancer screen company. In these interviews, we discussed the limitations of current treatments and also their view of good treatments.

Interviewing with the doctors we talked about targeting drugs: they are expensive in price, still have issues with stability and specificity. In addition, we talked about surgeries: Mastectomy and Lumpectomy. Lumpectomy (Breast-conserving surgeries) is considered to be healthier for the patients but it is not promoted in China, with a breast-preserving rate of only 22% compared to that of 80% in western HICs*. This is much due to lack of facilities and conserving mindset of many doctors.

The worst problem of all is lack of knowledge of breast cancer, only 5% of the population in China screens for breast cancer which caused most cases to be discovered during late stages, which is harder to treat.

Interview with Doctors, Breast Cancer Specialists:

Dr. Nong, from Peking University Shenzhen Hospital.

Dr. Zou, from Huazhong University of Science and Technology Union Shenzhen Hospital

Dr. Lu, from Xinhua Hospital.

 

When asked about treatments for breast cancer, Dr Nong spoke to us about monoclonal antibodies and ADC drugs. They are the two most frequently used drugs to treat HER2-positive breast cancer. She also revealed that the cost of targeted drugs is expensive, especially for certain imported drugs. The most commonly used monoclonal antibody is Trastuzumab. But according to Dr. Nong, the price of Trastuzumab is high, with approximately 5500 RMB each dose. Hoping to explore more about the cost of Her-2 positive breast cancer treatments, we connected with Dr Zou. He told us that Her2-positive patients who need targeted drugs might need 200,000 RMB in total, which is a significant amount of cost for general families. He also claimed that although antibody-conjugate drugs exhibited great effectiveness, there are certain limitations. Large molecules like antibodies have immunogenicity which are likely to trigger an unwanted immune response in bodies. Moreover, along with the transport, there is a possibility that drugs are disassociated with the antibody, which might accidentally kill normal cells. Aligned with Dr. Zou, Dr. Nong expressed her high expectations for a drug delivery system with high specificity and stability to come out in the future.

Figure 1.1 (Left) Interviewing with Dr.Nong at Peking University Shenzhen Hospital. (Right) Online interview with Dr. Zou

Besides drugs, we've also talked about surgeries: Mastectomy and Lumpectomy (breast-conserving surgery). Doctor Lu gave our team an online lecture about these two surgeries. In 2018, in breast cancer treatment, the proportion of breast-conserving surgery in China was only 22%, far lower than that of 80% in European countries as well as in the US. We also learned that doctors tend to avoid mastectomy which may result in appearance defects for females. Breast cancer doctors will seek the best way to do breast-conserving surgeries. However, these types of surgeries are coupled with radiotherapy to ensure all the breast cancer cells are killed.

However, according to Dr. Nong, the implementation of breast-conserving surgeries requires ideal pre-phase therapy to control the size of the tumor, such as adjuvant chemotherapy, radiotherapy, and endocrine therapy. The truth is that things aren't always done this way. Doctors that are more conservative in many Chinese second or third-tier cities lack the conditions to apply the breast-conserving surgeries, therefore more likely to take Mastectomy surgery as their first choice. Moreover, some small hospitals cannot provide sufficient equipment for radiotherapy or other methods to control the growth of the tumors, so they cannot perform breast-conserving surgeries as well. From another perspective of things, we learned that patients generally pay little attention to breast health from the doctors: they rarely check-in hospitals and are not aware of self-checking at home, which makes breast cancer a substantial potential risk for people. Overall, both of the doctors gave us an idea that it is crucial to develop an ideal pre-phase therapy in order to increase the rate of breast-conserving surgeries, which inspires us with our orientation.

Although there are many treatments for breast cancer, all three doctors claimed that ' early screening and early treatment is the best 'cure' for cancer. Breast cancer screening was free, but most people are unaware of it and don't check regularly.

Laboratory

After discussing with the clinical doctors, the initial version of our system had been formed. During the research, we were told of a substance called hemolysin (from our friends at SMS), which had the ability to kill cancer cells. However, the toxicity of the substance may cause safety issues which we quickly discovered in the following research. With our questions, we wished to contact professionals in the pharmaceutical field to solve our problems. Other than surgeries, drugs, however, aren't developed in hospital beds, they are tested in labs by researchers and scientists. Therefore, we started a series of interviews and discussions with specialists to talk about the research aspect of treating breast cancer.

Highlights

In order to develop and formulate our project, we interview specialists to learn about pharmacy research.

Limitations of current drug treatments lie in the level of toxicity and mark>specificity. We learned about how Antibody drugs tackle these issues and slowly formulated our project. We also interviewed pharmaceutical companies to learn about the process to validate our design, this includes in vitro tests using cancer cell lines. From a broader perspective, we learned that most pharmaceutical companies aim at improving existing platforms of drug development and few choose to develop innovative drugs.

Dr. Qiu

We interviewed Dr. Qiu (Clay Qiu), who is currently working in a pharmaceutical company in Suzhou, and specializes in areas associated with antibodies drugs.

At the beginning of our conversation, we pointed out that we wish to design a new drug to treat breast cancer and asked for the probability of using hemolysin as our “weapon” to kill the cancer cells. However, Dr. Qiu informed us that the toxicity of hemolysin was significantly high and merely no solutions could solve the problem, this was the reason why hemolysin wasn’t used in the pharmaceutical industry. He then advised us to shift our focus from drug innovation to the development of a new，well-established drug-delivery system, which will provide us with more opportunities.

From Dr. Qiu, we first learned that there are currently 4 types of targeting therapy for HER2 positive breast cancer (H2BC).

1. Kinase inhibitors
2. Antibody drugs
3. Antibody Drug Conjugates
4. CAR-T Therapy
(See more in Description)

We also discussed the relationship between drug toxicity and targeting ability of a targeting drug. Dr. Qiu told us that, as for a cancer targeting drug, stronger (more toxic) does not mean better. The more you do harm to the tumor, the more you do harm to the body. Many ADC type drugs were halted during clinical phase because their side-effects were too strong.

"We have to strike a balance, that is, how to avoid killing normal tissue cells while killing cancer cells as much as possible"

We also learned that Doxorubicin and Maytansine are two types of chemicals used in targeting drugs.

Furthermore, we continued our discussion on current obstacles in treating breast cancer. Dr. Qiu stated that, even for HER2-positive cancer patients, not all cancer cells overexpress HER2, thus killing only the HER2-positive cells might not be as effective we think.

We also asked Dr. Qiu about how drugs could remain intact during circulation inside the body, a factor to consider mentioned by our instructor Dr. Zong. Dr. Qiu told us that past targeting drugs, uses antibody which is a stable factor present in the body. An example is people using the FC domain of the antibody in ADC drugs, by binding chemicals onto this domain, their high affinity for each other would allow the drug to leave by exoplasmosis after being endocytosed by the normal tissue cells.

At last we asked the question:

What are the characteristics of the ideal cancer-treating drug?

Dr. Qiu's answer is summarized in the following:

"First is high specificity, this is the basis for increased toxicity of the drug. However, after decades of research in chemotherapy, scientists have tried many drugs and chemicals but so far we can conclude that monotherapies are just not enough to cure cancer; the micro-environment of the tumor tissue is too large to neglect drug resistance. Now, people are trying out combined methods, immunotherapies, and other therapies to compensate for the drawbacks of many treatments."

(Dr. Qiu also guided us during our idealation and laboratory stage, which you can find in Issues in Drug Development.)

Figure 1.2 Our online interveiw with Dr. Qiu.

Pharmaceutical companies

We also interviewed several pharmaceutical companies, to understand the current state of drugs as well as the process of drug production.

Innovent

Through our communication with Innovent, we learned that only a few of the company paid attention to developing new anti-cancer drugs in China. Most of the companies focused on chemistry manufacture and control, which is called the CMC department. This department utilizes existing drug producing methods and expands the quantity and quality within the existing platformed protocol, modified them to obtain the larger yields, higher quality controllable products.

Company N (Due to privacy agreements, we cannot show their name)

By talking with their consultant, we learned that there are two types of drugs: innovative and biosimilar products. Biosimilar products compete for lower prices, while innovative drugs compete for effectiveness.

We were also informed of the stages during drug development.

Pre-clinical, phase 1, phase 2, and phase 3. Which is used to test out the effectiveness and side effects of the drug. We used this information in the implementation section.

 

Questionnaire

Highlights

In order to confirm some of the problems mentioned by doctors and companies. We sent out a questionnaire. The results indicated a consistency for the need for cheaper drugs for breast cancer. The questionnaire also presented the public's lack of knowledge of breast cancer.

We also sent out questionnaires investigating the opinions on current targeted drugs; our audience included the general public, breast cancer patients, and their relatives.

In our survey, we wish to inquire about people's opinions on the price of the drug, as this is very related to the public as well as patients.

From our discussion with the doctors, we came to an understanding that drugs for treating breast cancer are expensive. We wanted to see how other people, people who live in a society (unlike us students) think about it. So one of the questions was about the affordability of breast cancer drugs. The results were reasonable: more than 70% of the patients’ relatives believe that the price is quite expensive that some households will be unable to pay the bill over a long time (Fig. 1), while more than 80% of the general public holds the same opinion (Fig. 2). So, it would be very understandable when 90% of our respondents said that they hope for a lower-priced drug (Figure 1.5)

Figure 1.3, 1.4 & 1.5.

The doctors we interviewed told us the current awareness of breast cancer were low, we still held questions about that, so also sent a questionnaire to gather information on the public’s understanding of breast cancer, including its precaution, transmission pathways, methods for breast examination etc.

Breast self-examination is probably the most convenient and efficient way for the diagnosis of breast cancer at an early stage, and with medical intervention, a high survival rate can be achieved. The examination itself is a rather simple task that includes rubbing the breast and checking for abnormal bumps, though from our results, more than 70 recent of the respondents do not know how to do the examination (Fig.4).

Figure 1.6.

We have also asked our respondents to identify some of the common methods for breast examination for preventing cancer that are done in hospitals, such as X-ray examination and B-scan ultrasonography. The results show the B-scan is the most widely known examination method, while more than 36%of the people could not identify any examination method (Fig.5).

Figure 1.7

For the transmission of cancer, our respondents were asked whether they think breast cancer can be passed by breastfeeding (It obviously cannot!) However, the result showed that nearly a third of the people chose the wrong answer.

Summary:

A lack of awareness of the examinations that could prevent cancer development was shown. Besides, there are some misunderstandings about breast cancer that should have been clarified. It is to our greatest pity that breast cancer, the disease that is potentially related to every woman and man, was currently not well understood by most of our respondents. Thus, we decided to include the publication of breast cancer and its prevention as a major part of our project in our Public engagement section.

Overcoming the Issues Within Drug Development

We've categorized the pharmaceutical issues we learned from our interviewees into Price, Specificity, Side Effects, and Stability. Below, we present our proposed solutions for each issue to formulate our design, all of which came up with our discussion with the experts.

Using Aptamers for lower price and specificy

Price

One of the main focuses of pharmaceutical companies is to lower the price of the drug. As this can be more appealing to the general public. However, even after over 30 years of development, the current price of antibody drugs remains high, as they are hard to produce or maintain batch to batch qualities.

For example, the current payment needed for the PD-1 in China is 30,000 yuan per year with health insurance, and the price for the Lapatinib and Trastuzumab is approximately 110,000 yuan for one period of remedy in China with health insurance. Which is not very affordable for most patients with this disease.

Reflecting on the problems of price, we went on to research about aptamers, an idea proposed by Dr. Qiu and mentioned in our discussion with Pharmaceutical Companies.

Aptamers are ligands that can bind to molecules, but instead of being composed of proteins (like antibodies), it is purely ssDNA. The weak interaction forces between the nucleotides allow them to fold into unique structures.Aptamers have many advantages over antibodies^[2]:

Characteristics	Aptamers	Antibodies
Immunogenicity	Low	High
Internalization	Fast	Low Efficient
Modification	Easily Modifiable	Hard to modify
Batch-to-batch variation	High Uniformity of Product	Low Uniformity of Product
Production & Development Cost	Low	High
Production & Development Time	Short	Long
Versatility	Wide Range of Targets	Targets with Immunogenicity

Table 2.1 A comparison between Aptamer and Antibody.

We also consulted with GreatBay_SCIE 2020, as their project is also regarding aptamers, though of different use. They advised us that we shouldn't focus too much on SELEX selection, as they've has already done so last year. They think the potential of aptamer lies in its ability to be modified and utilized easily; they advised us that spending time on how to implement the aptamer, improving existing aptamers perhaps would be a better option for us.

Specificity

Specificity is important, it is the foundation of targeting drugs. One of the most needed features of an ideal drug, from our interviews with doctors, is high specificity. Because this not only means that it has reduced side effects but also high effectiveness. Maintaining high specificity is key in our design.

To improve specificity even further, with our knowledge of cancer, and thorough research, we happen to encounter literature to make use pH-sensitive aptamer^[3], which we used in our design. This allowed our aptamer to gain higher affinity under low pH near tumor tissue, which indirectly increases the specificity of our drug.

A small interlude we encountered with aptamers...

We encountered an issue with aptamer synthesizing, as pH-sensitive aptamer has extra length, many of which cannot be synthesized or too expensive to synthesize (synthesizing an ssDNA strand of 113 require 2000 RMB which is roughly 310 USD), so we sought help from our advisor Dr. Zong, pointed out there are other ways to synthesize them ourselves such as using asymmetric PCR^[4], which we tried and succeeded in producing ssDNA strands ourselves (See in More in Lab Pages)

Using Nanoparticles for Less Side Effects and Better Stability

Side Effects

Chemotherapy although is the most mature type of drug treatment (developed in the 40s), it deals immense health damage to the patient.

Targeting drugs is the cornerstone to precision medicines. However, many current targeting drugs, especially ADC type, have issues regarding high toxicity. After talking with Dr. Qiu, we found out that there are currently, only two ADC drugs are approved by the FDA: TDM-1 and DS8201-a. Other drugs like MEDI4276 are all halted during the clinal phase due to high toxicity.

Intending to find a suitable payload of the drug that could lower side effects, we consulted Dr. Wei from the Northwest University of China, who is an expert in biomaterial and synthetic biology.

Dr. Wei suggests a nanoparticle drug delivery system, in which the drug was encapsulated inside a nanoparticle and the exterior side of the particle was conjugated with a factor that provides specificity for the targeted drug-aptamer.

We were informed that nanoparticles provide unparalleled advantages as a drug delivery system against tumors because of the EPR Effect (See more in Description & Proof of Concept) and its high customizability.

Dr. Wei points out that PLGA (poly lactic-co-glycolic acid) is a suitable material for the synthesis of our nanoparticle, for PLGA, first developed in the 1970s, is a polymer widely used in delivery systems, primarily because of its biocompatibility and degradability. It has been shown that the polymer can break down inside the body to produce non-toxic byproducts such as carbon dioxide and water^[5]. In addition, Dr. Wei also suggests that as an alternative route, liposome, a lipid bilayer nano-sphere with similar properties to PLGA would also be suitable for our project^[6]. So we decided to manufacture 2 types of modified nanoparticles: PLGA and Liposome.

We cooperated with Dr.Wei and Dr.Zeng, Dr. Shen to produce PLGA particles and Liposomes by using single emulsion-solvent evaporation and microfluidics technology respectively. (See more in Design and Proof Of Concept )

About Stability...

We raised this concern with Dr. Wei. Dr. Wei told us about factors such as PEG (polyethylene glycol) could be used to improve the plasma stability of our delivery system. PEG is a hydrophilic, flexible polymer that could be conjugated to the exterior of both PLGA nanoparticle and liposome^[5]. And once conjugated to the surface of our system, the PEG layer forms a hydrophilic coating that avoids the opsonization of plasma protein; besides, due to the transient, rapidly changing structure of the polymer, the immune system would have difficulties in modeling an antibody around the system.

Using Doxorubicin...

Another problem we encountered was that nanoparticles were only a delivery system, we don't actually know which drug to use is most effective or suitable. Dr. Lu advised us to use Doxorubicin (DOX), which is used many times in innovative drugs and past literature; it can be considered to be a model drug for testing our cancer-curing methods.

Feedback

At last, we presented our design of using aptamers-conjugated nanoparticle drugs to previous experts to receive feedback.

We presented to the doctors and although all three doctors are not experts in drug design, they all think an aptamer-nanoparticle-based drug delivery system is promising in the future. One doctor argued that the need for drugs to treat HER2-positive breast cancer have always been there. Secondly, currently, there are no targeted drugs using aptamers on the market, so our project is innovative.

The pharmaceutical company told us that our project is the front research of developing new pharmaceutical methods with potential. By using aptamer as the guider, this variety of ADC drugs is still not on market, there is still, a gap to be filled.

The other pharmaceutical company also advised us how to prove our drug to be valid. Although limited by iGEM, we cannot go into any clinical phase, the company introduced to us in vitro methods to prove the validity of our drug. They say that our validity test must include results that the drug is effective against cancer cell lines. For our current progress, they just advised us to consider things like cytotoxicity assay, pharmacokinetics, using algorithms to simulate potential toxicity. Though we only chose to do cytotoxicity assay due to time, their advice was invaluable.

Dr. Qiu then instructed us on culturing cells. He advised several cell lines for us to use and guided us through steps of subculture and preservation.

Figure 2.1 Our meeting with Dr. Qiu on Cell cuturing.

We cultivated our cells at Shenzhen University and the students there helped us carry out our experiments.

Modeling

To aid our experiment better, we also developed models to help us predict our product as well as infer important information such as the amount of aptamers we should use to help achieve better results.

Structural Modeling

For the structural modeling part, in order to make our model of aptamer binding with protein visible, we have used various modeling tools(Matlab, RNA Composer, mfold) to help us get the individual model of the aptamer and the protein. But we found it difficult to bind the models of the aptamer and the protein together. To solve this problem, we collaborated with the team ShenZhen_SMS to learn how to use Discovery Studio to attach the protein and the aptamer together. In return, we provided suggestions about Blender which helped them visualize their protein better and also help them to put their 3D models onto the wiki.

Mathematical Modeling

For the mathematical part of the modeling, Max Chen, a member of Greatbay_SCIE last year has provided valuable ideas of modeling, for example, he has mentioned that the distance between the aptamer should be greater than the diameter of an HER-II molecule so that the aptamer would not block the HER-II from binding onto it. The idea is further explored by our team by constructing the model of a liposome using the spherical coordinates and expressing the position of the aptamer using the coordinates, which allows us to analyze the optimum aptamer concentration mathematically, his idea has provided a valuable direction of our models.

To see more information on our modelling, click here to go to the modelling page.

Issues Remaining In Society

After receiving advice from the doctors, we were made curious about breast cancer itself and planned to investigate the current situation of this disease from a more comprehensive view. Therefore, we approached a breast cancer screening company and had a tour of their building.

Figure 3.1 Photo at Aisono company

From our talk, they told us that in China, only 5% of the female goes for breast cancer screening and in Shenzhen, only 150 thousand out of the 20 million people screens for breast cancer. One of the most important contributors to the present state is the lack of sonographers registered in China: only 140,000, which is far from enough to provide screening for the general public in China. Because of that, although the policy for a free screening of breast cancer exists, it is not heavily publicized.

This is where Aisono found opportunity and market. They developed machines to automate the process of breast cancer screening, using artificial intelligence to analyze sonography to be able to spot tumors during early development. According to them, even though breast cancer is now a widespread disease, if prevention and early screening techniques have gained significant advancement, it will no longer be a problem as the early stage is very treatable.

"We believed that the future of public health lies in prevention, not in treatment."

So, health awareness and the understanding of the fact that breast cancer is not dangerous if a constant examination and a healthy lifestyle are ensured. The thing is that not many people understand the importance of self-care and early screening. Based on this conclusion, we further initiated a lot of activities to engage the public. (see Below and Public Engagement)

Lack of awareness

Despite the solutions we proposed earlier to overcome barriers in drug production, we realized that curing cancer is incredibly hard after talking and interviewing with doctors and specialists. It's is not an acute disease but rather a chronic one most of the time. Diseases like breast cancer have no vaccines, thus the best way to prevent this disease is to live a healthy life, or treat it as early as possible. However, the current state of public knowledge with breast cancer worries as, as seen from the questionnaire. Hence, we wish to make awareness about breast cancer. (Seen more in our Education & Public Engagement Page)

Talking with the Chairman

We mentioned this current situation of breast cancer in China with the chairman of Pink Ribbon. She agreed with the idea that people learned a little about this well-known disease. Not only did people have limited knowledge about the prevention of breast cancer, but they also lacked information about the symptoms of breast cancer at the early stage. The chairman told us a story of a young woman who was sent to the hospital after she suddenly passed out during her working time. At this moment, she had a thorough medical examination and eventually found out that she had breast cancer. Before this accidental event, she did not realize that the abnormal symptoms of her body that she usually ignored indicated this disease. The chairman emphasized through this story that modern people were lacking a clear understanding of their body and they did not do a regular physical examination to help them to learn about their real health situation, especially about their breasts. The lack of consciousness of prevention and understanding of the body leads to countless tragedies.

Figure 3.2 Our visit to Pink Ribbon

Further Research with Help of Questionnaire

After talking with the chairman, our members discussed this existing problem and what caused it to happen. Our primary estimation was that people, especially females, lacked a kind of consciousness to learn more about their bodies. Most of them were ashamed of the weird change of their body and did not want to mention it even with their intimate friends and family members. This made them fail to go to the hospital at the right time and miss the right time for treatment.

We handed out a questionnaire to find out about the problem of women's identity in current society. And we would like to share our results.

One of the most representative information we had was, in most families mothers spend the most time with their children, while no family says that the father spends the most time with the children. This is also reflected during our conversation with the patients, as they think that pressure from family is one of the greatest sources of stress (which leads to breast cancer).

Figure 3.3 Some indicative questions on our questionnaire.

In terms of status, many people say that now women have much high status, but still not enough, as the issue of sexism present in society is a severe issue.

However, we think that this questionnaire was flawed. As we realize now, we think that we should have asked more questions about the situation of their family (like Figure 3.2 Left) to reflect directly on the issue instead of more subjective questions of how they think about it. Nevertheless, the questionnaire still reveals the issue of gender inequality.

Breast and Bra

The forum with Ms. Lucy reminded us of the easily neglected part of a female’s self-consciousness— our body itself. We all understand that the breast is an important symbol of female sexuality. However, do we really what is breast and how should we correctly perceive this organ of our body? The boys and girls of GreatBay_SCIE would like to share what we have learned with you.

Figure 3.4 Our visit to Pink Ribbon

First of all, women have 4 different types of body shapes, A, V, H, and X, depending on the circumferences of a woman's chest, waist, and hips. For breast, we have six categories in terms of shape— disk-shaped, conical, round, spindle-shapes, droop I, and droop II. These shapes are present in all age groups but some transformations might happen, such as turning from spindle-like to droop II. Some young girls nowadays refuse to wear bras for a sense of freedom or comfort. However, that is not a healthy way to treat your body.

Figure 3.5 Different types of breast.

The suitable bra varies from individual to individual. Out of three types of bras—full coverage, 3/4 coverage, and 1/2 coverage—the conical shape and droop II shape prefer the first while the other four prefer the 3/4 coverage bra. The 1/2 coverage is just for special occasions, for example, weddings. After deciding the bra type, we then have to choose the right cup. Measuring both the upper chest circumference and the lower chest circumference in the correct way can ensure that you have chosen the most healthy size of the bra. Once you have decided on the cup, try it on and see whether bra rims stick on your body and whether your breast gets oppressed. Apart from the things above, make sure you have taken your bra off while sleeping to relax after a tiring day.

Figure 3.6 Measuring chest is one of the important steps for choosing bra.

After choosing the right bra, we have to take good care of it. Don’t wash it with extremely hot water and don’t put it under serious sunshine — the improper care of your wear might increase the risk of breast cancer because of the material and chemicals in your bra.

Also, learn to take care of your breast by massaging it. Follow the picture below, do it in routine to keep your breast in good shape and healthy condition.

Figure 3.7 Massage method for breast health

Due to an increase in risks like pressure from family and work, as well as the pollutants, the incidence rate of breast cancer increases greatly. Therefore, knowing the way to self examine yourself is exceptionally important. According to Ms. Lucy and Doctor Zou, we have been introduced to the process of self-examination. First, make sure your breast is in the correct shape without any distortion. Some signs like the nipple being pushed inward could be a dangerous indication. Then, see whether there is liquid coming out of your body or the nipple, no matter in what color. Apart from the visible changes, feel them with your hands. Use the pads of your hands to press your breast in a circle with the whole coverage to make sure that there is no hard lump that moves around under your skin. Do that on a regular basis, and go to the hospital for further examinations like mammography. Breast cancer is not as scary as we perceived, so look for treatment as early as possible, then it won't lead to any serious consequences.

Last of all, ensure yourself a positive mood and healthy lifestyle— diversified diet, regular sleep, and constant exercise—keep you healthy from all perspectives.

Documentary

Thanks for the supports from the Pink Ribbon, we had an opportunity to hold an interview with three convalescent patients who had experienced fighting with breast cancer in the past. During our conversation, they discussed how large the impact of the disease had on their lives, as well as their self changes. We surprisingly found out that all of the volunteers stated that their mindsets were significantly changed after their realization of spending too little time taking care of themselves. Some of them were busy with their families, others dedicated to their careers.

Figure 3.8 Behind scene of our conversation with patients

During the treating process, the woman’s self-awareness among the volunteers had been aroused. They started to reflect on the past lifestyles, and more significantly -- the patients discovered that their self-identities became blurred in the previous years. As time progressed, they gradually embraced the idea of the importance of “ ego” towards a woman or an individual. Developing personal hobbies and social circles had a positive impact on mental health as well as the promotion of the treatment for breast cancer. In addition, the volunteers also shared their perspectives towards the current situations of breast cancer patients and how social attitudes would affect the group of people. From the interview, our team members obtained a more comprehensive perception of the orientation and scenarios of our project whilst noticing that the improvement of awareness of breast cancer was crucial for society.

Our Interview with Breast Cancer Patients↓

Reference

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