Cancer Awareness

Cancer Awareness is vital in battle against cancer. Cancer is one of the leading cause of death. It is a disease that affects people from all walks of life, it does not discriminate against race, gender, or age.
Dr Shah encouraged the audience to empower themselves by learning more about cancer, as well as preventive measures and the importance of screenings for early detection.

Chemotherapy FAQs

FAQs (Frequently Asked Questions) about “Chemotherapy”

What can chemotherapy do for you?
Depending on the type of stage chemotherapy can be used for different goals;
1. Cure Cancer
2. Control Cancer
3. Relieve symptoms

Can Chemotherapy be used with other treatments?
Yes. Chemotherapy can be used alone or with other treatments like surgery, radiation therapy or other medicines, e.g. biological therapy or targeted therapy.

What are factors affecting choice of chemotherapy drugs?
1. Type of cancer & Complete pathology report
2. Stage
3. Effect of cancer on your normal body functions
4. Any previous illness e.g. diabetes, heart disease

Where will I get chemotherapy?
Hospital’s outpatient department, doctor’s clinic or hospital.

How is Chemotherapy given?
Most are given Intravenously. Some can be given by mouth.

How frequently will I get chemotherapy?
Depending on the type and stage of the cancer. Usually given for 1 to 2 days every 1-3 weeks. There is a cycle, where there is a treatment period and then a rest period (necessary for building up healthy cells).

How will I know if my chemotherapy is working?
By the opinion and advice of your doctor based on your responses, blood tests, sonographies, CT scans and other tests. Side effects are no indication of the result.

What are the side effects of chemotherapy?
Side effects depend on the drug used. Today with our methods, 90% of patients are able to complete treatment without getting admitted to hospital even once. Hair loss which is most worrisome to patients, is temporary and does not happen with many new medicines. Same is true for other side effects.

What are NonChemotherapy Medicines?
Several medicines used to treat cancer are not chemotherapy. Many of them are new. Some of them are also known as TARGETED Therapies. Some of them are taken by mouth, some by intravenous route. Most of them are better tolerated. They are used in treatment of several cancers such as breast, mouth and throat, lung, intestine, leukemia, lymphoma.

Is operation always required?
Operation was the first step in treatment of most cancers in the past. Now many cancers can be treated without operation, or are treated with medicines first to reduce extent of surgery. Some examples are breast, mouth and throat, esophagus or food-pipe, cervix, lung, rectum, bone.

Stem Cell Transplant

ABC of Stem Cell Transplant – Role in Blood Disorders

Stem cell transplant is an exciting area of medicine, and currently a topic of hot debate at several fronts. It holds a great promise to ease or cure many ailments. Research is ongoing in several areas. This is an established treatment, however, for many years in the field of blood disorders (Hematology), such as leukemia, lymphoma, myeloma, thalassemia, aplastic anemia and others.

Stem cell or the “Basic Cell” is a simple concept, based on the fact that all humans are made from a single cell. This cell gives rise to all body tissues and organs. Precise controls for the same are largely unknown. However, it has been found that even in adult body, there are cells which can differentiate into any type of cell, and hence potentially can recreate any tissue. This is the premise of stem cell research. If we can find these cells and understand their controls, we can recreate and replace injured or lost tissue e.g. heart attack, stroke/paralysis, diabetes, arthritis, liver or kidney damage…

However, it is not easy as it sounds e.g. when we inject stem cells into an area of heart, whether they will grow into heart muscle cells or nerve cells or blood vessel wall cells and in what proportion, is currently not controllable. All of the above mentioned areas are under active research, but none except hematology is confirmed beyond doubt and therefore still remain experimental.

Only established role is in Hematology where it is in use for decades. We will talk only about the established area. In spite of so much need based on existing recommendations and patient numbers, there are very few centers in India, performing regular transplants for blood disorders. According to one estimate, there are only about 300 transplants per year in India. Last year, we have done 10 transplants.

For comparison, we can see European data, where every year about 30,000 transplants are performed. Our need i.e. in India is at least 50,000 transplants per year, likely much more. Cost of transplant in India is one tenth that of the cost in Western countries. However, because there are few good centers of excellence in this field, many people still go out of country for this life saving treatment.

Few case examples will help to understand the impact of this method of treatment.
A six year old child has undergone 8 months of chemotherapy for Hodgkin’s disease. Mother reports that his lymph glands in neck never went away completely. They started increasing in size in next couple of months, and they came to us. This is primary refractory Hodgkin’s disease, and with any further traditional chemotherapy, chance of cure is nearly zero. This patient underwent high dose chemotherapy followed by autologus hematopoietic stem cell transplant, and is now in remission i.e. no sign of disease anywhere with whole body CT scans, even after more than one year. He has about 50-60% chance of being cured.
A 29 year old man, only son, who has a young daughter and wife is pregnant, comes with a white cell count of 180,000 (normal count should be within 4000 to 10,000). He is diagnosed to have acute myeloid leukemia, a type of blood cancer. He is put in remission with standard therapy. Risk of recurrence is high and they want to do the best possible to increase chance of cure as much as possible, with reasonably safe and proven method. He underwent high dose chemotherapy followed by autologus hematopoietic stem cell transplant. He has about 50% chance of being cured.
An 8 month old child is diagnosed to have Thalassemia Major. Child is undergoing regular, monthly blood transfusions, and is doing well. She is a very sweet, bright child. Over next year or so, there is increasing frustration in this educated family that this treatment is not curative and that she will survive only till age of about 20 to 30 years. They search for a better treatment, and undergo matched allogeneic stem cell transplant from her older brother. She is now transfusion free and will have a nearly normal life.

Stem cell transplant in Hematology is an established therapy. Beauty of this procedure is that there is no surgery/operation involved in this whole process, unlike kidney or liver transplant. Patient is kept in his room through out the hospitalization and is otherwise reasonably well i.e. talking, eating, taking walks every day. Patient has to stay in the special unit, prepared to reduce infections.

The procedure serves mainly 3 purposes:

Allows use of very high doses of chemotherapy, which ablate bone marrow. Without stem cell support, marrow will recover after a very long time, resulting in high death rate from infection or bleeding. Infused stem cells provide early recovery of blood cells, cutting down the risks of myelosuppression. Thus it is a form of “Supportive Therapy” and not a treatment of cancer by itself. This is the case in autologus (self) transplants.

Some “graft versus disease activity”, in allogeneic transplants done for hematological malignancy, especially evident in chronic myeloid leukemia.

Replacing a missing gene e.g. in thalassemia, sickle cell disease, and various other genetic disorders. These are diseases where a person is otherwise normal, except for one missing gene, and replacing that gene is curative.

Hematopoietic Stem Cells:

They live in the bone marrow i.e. cavity inside the bone. These cells constitute less than 1 in 100,000 in bone marrow cells. They look like small lymphocytes and cannot be distinguished from other normal cells by morphology. They are identified by special techniques such as immunophenotyping using flow cytometry, which uses different markers, most notably CD 34 in this case. These cells are capable of self renewal as well as production of progenitor cells which differentiate into mature blood cells.

How are they collected:

Since during normal state they are very few in numbers, bone marrow is stimulated with use of growth factors with or without help of chemotherapy. This leads to increase in their number. Then they can be collected from either bone marrow or peripheral blood. Their number in blood can be counted daily and collection is done at right time.

Collection is done using a procedure called Apheresis, almost similar to dialysis done for patients with kidney failure. Patient or the donor is on a special chair or bed for about 6-8 hours per day, for 1-4 days. During the apheresis procedure, he/she can talk, eat, watch TV, read normally. Procedure is nearly risk free. Also, there is no permanent loss from body i.e. unlike kidney or liver transplant, donor is not losing anything permanently. Stem cells are recovered by body in few days time. Because of such safety of this procedure, and because this is such a life saving treatment, over 15 lakh people have registered themselves as voluntary donors in USA alone, in a national registry. Unfortunately, there is no registry in India.

Storage: Total number is then counted and storage is done after adding special chemicals and at very low temperatures (at minus 80 degree celcius or in liquid nitrogen) to maintain their viability for a long time.

When needed, the bag full of stem cells and additive liquids is thawed and transfused with some specific precautions (almost like a blood transfusion). So, once again, there is no operation involved in this type of transplant.

Sources of Hematopoietic Stem Cells:
Bone Marrow
Peripheral Blood
Cord Blood

When stem cells are collected from one’s own body, it is Autologus Transplant.
When stem cells are collected from someone else’s body, it is Allogeneic Transplant.

Cord blood stem cells have certain specific advantages and disadvantages. Cord blood registries are now available for use in certain conditions, and more registries are up coming.

Indications:

Autologus: mainly different types of blood or lymph gland cancers

Non Hodgkin’s Lymphoma – For recurrent/resistant cases, it is standard therapy and in most such cases, it is the only curative option.
In some high risk cases, where chance of recurrence is very high based on known prognostic criteria, it can be done upfront.

Hodgkin’s Lymphoma – For recurrent/resistant cases, it is standard therapy, and in most such cases, it is the only curative option.

Myeloma – Although not curative, it is standard treatment as part of initial therapy, as it prolongs survival substantially. It is perhaps the commonest indication for transplant in western countries.

Leukemia – Increasingly being used for Acute Myeloid Leukemia as part of initial therapy, to increase chance of cure in this dreadful disease.

Allogeneic: several indications

Thalassemia Major
Several other genetic disorders, especially with single gene defects
Aplastic Anemia
Chronic Myeloid Leukemia
High risk AML (acute myeloid leukemia), relapsed AML
Relapsed ALL (acute lymphocytic leukemia)
As last resort in several advanced or refractory hematological malignancies, where small but significant percentage get cured or have long term survival e.g. follicular lymphoma, CLL, myeloma…

Contraindications:
None is absolute, all are relative, since in many cases risk of underlying disease is much higher than risk of performing transplant.
Age: not over 60-70 in most cases, however this is changing with better conditioning regimens and supportive care.
Poor visceral organ function e.g. significant disease of heart, lung etc
Lack of a good matched donor – once again, this is slowly changing as well, with increasingly mismatched transplants now being feasible.

Risks:
These transplants are done with high doses of chemotherapy and other highly immunosuppressive agents entailing risks of the same, as well as risks of graft versus host disease. Most common risks are related to infection, bleeding, chemotherapy related organ injury e.g. kidney/liver/lungs, graft versus host disease.

Mortality of transplant has reduced significantly, and is now in the range of 5-10% for Autologus Transplant and about 10-30% for Allogeneic Transplant, depending upon indications and host factors.

Cost:
Mainly related to use of blood products, antibiotics/antifungals etc, isolation unit, specially trained staff, chemotherapy/immunosuppressive agents, investigations, stem cell collection and storage. About 5 lac for Autologus and about 10 lac for Allogeneic.

Indian Perspective:
We see comparatively younger patients, almost by a decade, with respect to western data. These are the patients who can tolerate aggressive treatments like transplant better. Newer medicines are often very expensive and add a smaller increment to survival e.g. for non hodgkin’s lymphoma, Rituximab is a good drug. At a cost of about 6 lac for the course, it adds about 15% increase in absolute survival when used upfront with chemotherapy. It does not cure relapsed lymphoma. However, at a cost of 5 lac, autologus transplant can cure much higher number of relapsed lymphomas. It should be investigated for upfront therapy of high risk lymphomas in India. Such study is unlikely to come from Western countries, since they can afford more expensive medicines today, and will not take such a risk. Same is true for many other diseases mentioned above.

Thalassemia major has a very good cure rate with transplant, and we have a very high number in India, especially in Gujarat.

Research in stem cell technology is likely to further improve safety profile of these therapies, and also reduce cost.

BREAST CANCER PART-14

This article highlights on post treatment follow up and importance of secondary prevention

Que: It was interesting to note that there are many subsets of stage 4 cancer and that many patients live for a long period. Also, concept of goal setting, observation only in some patients, use of hormonal therapy primarily, use of single agent chemotherapy, place for targeted therapies and other issues were quite informative and provided good guideline.
Ans: Thank you for summarizing it so well. Please do not forget the importance of proper early therapy, both local and systemic, at first diagnosis, to prevent metastatic disease. Hope the readers will also advise people about advantages of early diagnosis, and of course prevention, the ultimate goal.

Que: What about secondary prevention i.e. what should a woman do who has completed treatment for breast cancer? What lifestyle, what tests, what follow up?
Ans: This is a very important question. A woman is very concerned at the end of initial intensive treatment such as chemotherapy, surgery, radiotherapy. Some of them will go on to hormonal therapy, and some will have no more active treatment.
Knowing that there is a chance of relapse, more or less depending upon stage, makes them very anxious. Women want to know what they can do to prevent relapse, or at least make an early diagnosis in case cancer were to come back.

Que: What can they do to prevent relapse?
Ans: Most important step is to take regular treatment if advised, such as hormonal therapy, or in some cases herceptin. Apart from this, it is known that maintaining weight close to their baseline, regular exercise, and reduced dietary fat intake reduce risk of relapse.

Que: What can they do for early diagnosis, in case of relapse?
Ans: This is an area where a lot of unindicated tests are done. Most people think that frequent scans and blood tests will lead to early diagnosis and will make them live longer. Unfortunately this is not true. Only things that help in follow up are: monthly self examination, regular examination by doctor (initially every 3 months and then increasing period), annual mammogram of remaining breast (both if lumpectomy), and early reporting of new persistent symptoms. Later should lead to specific tests e.g. new persistent abdominal pain should be evaluated by related blood tests and sonography or CT scan. Some recommend annual chest x-ray.
It has been studied several times and it is very clear that frequent scans and blood tests, including tumor markers, do not lead to early diagnosis that translates in to prolonging life or saving life. In fact, most of the time it leads to false alarms, leading to unnecessary biopsies or further tests and anxiety. I have seen many such patients. All guidelines also recommend against such tests in asymptomatic follow up patients.
We give a follow up chart to our patients, where one of the lines is “Bone scan, Tumor markers, Ultrasonography, CT scan are not routinely recommended”.

BREAST CANCER PART-13

This article highlights about treatment of stage 4 breast cancer

Que: What about very advanced cases i.e. stage 4 breast cancer? Can we cure any of them?
Ans: Important issue. As you know, many of our patients are still diagnosed in stage 4, and many relapse after initial treatment and go on to stage 4. First of all, however, I would like to clarify that stage 4 does not mean end of road.

This is a very heterogenous group of people. Technically anyone with a cancer that has spread outside of breast and regional nodes has stage 4 disease. But a patient with only a few bone metastases may live for several years, whereas one with many brain metastases may not survive few months.

With available treatment options, there are rare patients who are completely free of disease or live for over 5 years even after diagnosis of stage 4 disease.

Que: I always thought that stage 4 means few months survival and nothing will work. And that there are subsets of stage 4?
Ans:.Yes. This is true for every cancer to some extent, but the variation is extreme in case of breast cancer.

Que: So how do you treat stage 4 breast cancer patients?
Ans: Goal setting here is very important. Since this is rarely a curative treatment, goal is to provide symptom free period mainly, and extend survival to some extent. Therefore, hormonal therapy when ER/PR test is positive is the treatment of choice, and as we have seen earlier, now there are many options.

In fact, patients with few metastases and no symptoms are frequently left alone without treatment and only close observation, that too mainly clinical observation. Remember the goal is to make patient symptom free and if there are no symptoms, there is often no reason to treat for many months!!

Next group of drugs is targeted therapies like Herceptin, Avastin, Lapatinib etc, however they are very expensive. But when feasible, they are useful and well tolerated.

Last option is chemotherapy, where more than 10 drugs are available which can be used in many different ways, from weekly to 4 weekly, alone or in many different combinations. In general, single drug should be given rather than a combination of chemotherapy drugs. Oral medicines are also available. Duration of therapy is generally 4-6 months at a time with chemotherapy, and then there is a break period, until relapse of significant symptoms or impending risk of serious symptoms.

Once again I would like to stress that metastatic or stage 4 cancer is largely incurable and we can provide some reasonable quality of life. But early diagnosis, and good postoperative therapy to prevent stage 4 cases is the best strategy. That is why we stress so much on proper evaluation by all related specialities at first diagnosis of breast cancer, to decide right strategy for each and every patient.

BREAST CANCER PART-12

This article highlights about other advances in breast cancer therapy such as in hormonal therapies and radiotherapy.

Que: Are there any other advances that women can benefit from in this increasingly common cancer? I have heard about or met several patients with breast cancer, many of whom were treated several years ago, and are now free of disease leading a normal life.
Ans: I agree. There are many such patients with breast cancer. We do not have numbers for India, but in USA alone, there are more than 10 lakh breast cancer survivors. This itself is an evidence that one can get very positive results in breast cancer, especially if diagnosed early.
And yes, there are two other important advances in treatment i.e. in hormonal therapy and in radiotherapy.

Que: You mean there is something more than Tamoxifen?
Ans:. Yes, after so many years, there are aromatase inhibitors i.e. arimidex, letrozole, and exemestane. These drugs are more effective compared with tamoxifen, and are already in widespread clinical use for over 5 years. Also, they are not associated with two uncommon but serious side effects of tamoxifen i.e. deep vein thrombosis and uterine cancer. However, they can be used only in postmenopausal women.

These drugs are so effective that they are used as sole preoperative treatment in elderly frail women, with good tumor shrinkage without chemotherapy. They have also replaced tamoxifen in most cases for postoperative treatment.
Also available are estrogen antagonist Fulvestrant, LHRH agonist Goserlin and few others. These are mainly used in metastatic cancer today.

Que: What about Radiotherapy? Is that also getting better?
Ans: Of course. With advances in software and hardware, radiotherapy precision has improved considerably. Hence now we are able to deliver more dose, at the same time with less side effects. Exposure to heart and lungs is markedly reduced. Because of these advances, radiotherapy now adds to survival, especially so in patients with positive axillary nodes. Radiotherapy should be given after systemic chemotherapy in almost all cases. Sandwiching it between chemotherapy cycles is no longer practiced.

Remember also that lumpectomy (partial breast removal), also known as breast conservation surgery is not possible without radiotherapy. With improved techniques e.g. IMRT and IGRT, cosmetic results of post BCS radiotherapy have improved significantly. This is an important aspect in widespread adoption of lumpectomy.

BREAST CANCER PART-11

This article highlights about most advanced developments in this field, with targeted therapies like herceptin, trastuzumab, lapatinib, and how they are changing the way we treat breast cancer.

Que: Even in LABC good results are possible, with addition of preoperative chemotherapy. However, Her-2 test has been mentioned few times in this series, and also you mentioned Herceptin in tenth part. Can you tell us somewhat more about that?
Ans: As we discussed last time, breast cancer can be treated with chemotherapy, hormonal therapy, and these newer so called TARGETED therapies. These are so called as they have a more focused action on specific part of cancer cells, unlike chemotherapy which acts on several aspects of cell functioning, and hence has more side effects.

Her-2 receptor on breast cancer cell surface provides these cells ability to grow much faster, and survive in body longer. This knowledge led to development of a drug directly attacking this receptor i.e. Herceptin(Trastuzumab). It is the first such drug in breast cancer. About 25% patients have cancers that test positive for Her-2. Only these patients benefit from use of this drug.

Que: That sounds exciting. Do you mean to say that this drug has no side effects? Do we need chemotherapy then?
Ans:. I definitely share your excitement. This drug has improved results remarkably for patients with Her-2 positive disease, who otherwise had a poor prognosis. In fact, results are so good that it can be used alone without chemotherapy to treat patients with very advanced cancers.

However, in stage 1-3, it has to be combined with chemotherapy to achieve the best results. In stage 3 for example, when added to preoperative chemotherapy, many cancers are not found at time of surgery i.e. a very high rate of pathologic CR is seen, and this translates into good chance of cure. In other stages, it is given after surgery, initially with chemotherapy, and then for a long period after chemotherapy is over. In these studies, it reduces risk of relapse by 50%, which is very good by any standards, and very few drugs in oncology give such results.

With regard to side effects, it is extremely well tolerated, and can be easily given to even patients with significant weakness. Few specific precautions are required.

Que: Why don’t we have more such TARGETED therapies?
Ans: Actually we do, but it is a recent development, with difficult technology and the drugs are still expensive. Another target is VEGF which provides tumors with extra blood supply which they need to grow big. Avastin (Bevacizumab) is a drug which blocks action of VEGF and shrinks tumors. It is used in several cancers now, including breast, lung, colorectal, liver, kidney and others. Also, just like Her-2, there is a Her-1 receptor. Lapatinib is a drug that blocks both these receptors, and is in tablet form.

BREAST CANCER PART-10

This article highlights about management of locally advanced breast cancer with preoperative chemotherapy, surgery, postoperative chemotherapy and radiotherapy.

Que: What is the prognostic features which help you in deciding treatment plan.
Answer: I am glad. It is really important for doctors and patients to realize that removing a cancer if often not enough. Since cancer is a systemic disease in many cases, from the time diagnosis is made. Do you know that by the time a cancer is visible by scan or palpable, it already has millions of cells, and several have frequently spread to other parts of the body but are just too small for detection. Circulating cancer cells have been found in blood in patients with very early stage breast cancer.

Que: This means that we have to try very hard to make early diagnosis. Isn’t it?
Ans:. Yes, of course and that is going to give us the best results. Unfortunately the reality in India is different today. And a large number of patients are diagnosed in stage 3 i.e. locally advanced breast cancer (LABC).

These are patients with either large primary tumors more than 5 cm in size or invading local structures, OR those with matted or fixed axillary nodes or nonaxillary nodal involvement.

Primary surgery in LABC is often incomplete and risk of leaving disease is high. Therefore, preoperative chemotherapy is strongly indicated. Same regimens used for postoperative chemotherapy are reasonable. Responses are seen in majority of patients, allowing complete proper surgery. In about 50% patients, response is dramatic and in about 25% patients no tumor may be found at surgery, known as pathologic CR.

If patient has Her-2 positive disease, a drug called Trastuzumab (Herceptin) should be added. When Herceptin is added, response rate improves remarkably.
Elderly patients with hormone receptor positive disease can be treated with preoperative hormonal therapy e.g. aromatase inhibitors.

Que: Do these patients need more radical surgery?
Ans: Standard surgery for these patients is same as others i.e. modified radical mastectomy and axillary dissection. However, since chemotherapy responses are so much better nowadays that some patients become eligible for only lumpectomy.

All these patients need adjuvant radiotherapy. Radiotherapy should be done after completion of chemotherapy.

BREAST CANCER PART-9

This article highlights about surgery for early stage breast cancer i.e. stage 1 and 2 cancers, and when do we need additional therapy e.g. chemotherapy.

Que: How do you decide treatment for early stage breast cancer?
Answer: Treatment decisions are of course fairly complicated. But I can give some general guidelines. As you may recall, in seventh part, we divided patients in 3 categories – early (stage 1,2), locally advanced (stage 3), and metastatic (stage 4).

For Early Stage i.e. stage 1 and 2 patients, traditionally surgery has been the initial treatment. There is a wide variation in these patients, however, with regard to tumor size, lymph node status, breast size and other parameters that go in to deciding treatment.

Que: Can you tell us what is the commonest way of dealing with this stage?
Ans:.Surgery is the commonest initial treatment. Most patients in India undergo MRM i.e. modified radical mastectomy. Whole affected breast is removed along with nipple-areola complex. Axillary dissection is routinely performed with MRM, to remove regional nodes in axilla. Later also allows accurate staging of locoregional spread of disease, which is an important aspect of deciding further treatment.

Those patients with truly early disease i.e. small tumor (<2 cm), no lymph nodes involved and no poor prognostic features do not require any further treatment. All others require some treatment after surgery, as their prognosis is not good with only surgery. For example, as a rough guide, chance of relapse after surgery is about 1% per 1 mm increase in size of tumor i.e. if tumor is 25 mm, there is 25% chance of recurrence after surgery. If tumor is 50 mm, there is 50% chance of recurrence. If lymph nodes are positive, there is an additional risk. This is a very high risk, and obviously additional treatment is required. Surgery alone is not enough. However, it is important to understand that a good surgery provides very important initial risk reduction. Complete tumor clearance with good margins, removal of at least 6 (preferably more) axillary nodes, removal of all residual breast tissue (especially in case of large tumor size) are critical.

Que: Are there any advances in surgery? Is something less radical possible?
Ans: Yes, there is something known as lumpectomy or “breast conserving surgery”, where only the tumor is removed with sufficient margins. Whole breast is not removed. In fact, about 50% of surgeries in USA are now BCS. Awareness and trained surgeons for this option are limited in India. Radiotherapy to remaining breast tissue after lumpectomy is must.

Preoperative chemotherapy is routinely used to make patients suitable for lumpectomy, but only if they fulfill certain criteria.

Sentinel lymph node biopsy is a technique which reduces amount of axillary dissection, in patients with very small tumors and clinically normal axillary nodes. Very few centers routinely offer this option. Its impact on clinically meaningful parameters is anyways questionable.

BREAST CANCER PART-8

This article highlights about evaluation of breast cancer, essential for proper staging and for making critical treatment decisions.

Que: Many patients in India are diagnosed in advanced stages. Is this limited work up sufficient for them?
Answer: You are right. A large number of our patients come in with large tumors, and/or obvious axillary nodes. Most of these patients would be classified as Locally Advanced Breast Cancer – LABC, i.e. stage 3. These patients need all the tests noted for early stages. In addition, they need tests to make sure that they do not have metastatic disease already. Such additional work up includes preferably CT scan of chest and abdomen, or at least an abdominal sonography, bone scan. Any symptomatic area should be evaluated further e.g. neurological symptoms or headache should be evaluated with MRI of brain.

Stage 4 patients, or those with established metastatic disease need tests to establish total tumor burden i.e. all the sites where tumor has spread, and to decide areas which need priority treatment. e.g. if there are brain metastases, first treatment is generally directed to brain. Similarly bone scan positive sites need x-rays to see if there is imminent fracture risk, especially important for weight bearing areas. PET scan is increasingly being used in this scenario. Tumor markers are also helpful in such a case, as they allow easy follow up e.g. CEA, CA 15-3, CA 27-29 (last is not easily available in India).

Of course, ER/PR/Her-2 status are very important to check, if not known from past, or if relapse is after many years.

Que: Thank you Dr. Shah. So, most of the evaluation is Radiological, trying to determine stage and spread of disease.
Ans: Yes, but do not forget the importance of pathology evaluation. Even before surgery, it is very important. A good biopsy is necessary to determine histology, grade, neurovascular invasion, and ER/PR/Her-2 status. Since patients with locally advanced breast cancer are treated with preoperative chemotherapy, detailed pathology evaluation is important presurgery. After surgery, this evaluation may not be feasible in many cases. For this reason also, FNA should not be used in LABC evaluation, rather a trucut or wedge biopsy.

Importance of a good histopathologist cannot be overemphasized. This is even more important with newer methods like IHC. Even in US studies, there is a 20% discordance rate (results not matching) between community hospitals and university hospitals for ER/PR/Her-2 tests. Since these are crucial tests in evaluating therapy options, they should be performed only in quality, high volume centers. No other tests e.g. ploidy, or S phase fraction are useful in clinical practice, and need not be routinely tested for. FISH testing can be used if Her-2 test is equivocal by IHC.

BREAST CANCER PART-7

This article highlights about evaluation of an early stage breast cancer.

Que: What kind of work up do you advise, and how do you decide treatment for breast cancer patients?
Answer: Oncology is one branch where multidisciplinary evaluation of a newly diagnosed cancer patient is vital. Since cure rates can improve significantly and advances are rapidly occurring in this field, patient should benefit from integration of all modalities.

Goal of the initial work up is to determine stage, and certain prognostic/predictive parameters. Additional goals are to determine patient factors such as comorbidities, as well as patient’s choice and socioeconomic factors. All of these determine treatment, for example, choice of lumpectomy versus mastectomy is influenced by stage, patient’s personal choice, absence of comorbidities that preclude radiotherapy, ability and reliability to complete course of radiotherapy which in turn may be related to distance from radiotherapy facility, patient’s understanding of importance of adjuvant radiotherapy and so on…

Similar decision making is required at most steps, and treatment has to be tailored to get the best possible results.

Que: Thank you Dr. Shah, it is interesting to note that such detailed analysis is required, including even patient’s choice and social factors. Do you need a large number of tests?
Ans: Most of this is determined by good old history and examination. Number of tests needed are few. For a general understanding, patients are divided into three groups – early i.e. stage 1 and 2; locally advanced i.e. stage 3; and metastatic or spread disease i.e. stage 4.

First we will talk about so called early stage, where we need only a chest x-ray, Hb, TC/DC, platelets, SGPT/SGOT, alkaline phosphatase, and basic preoperative tests. Bilateral mammogram should ideally be done, but it alters management plan in a very small number of cases, and hence it is ok to exclude if not available in certain centers, as is the case outside most large cities.

Sonography may possibly be used where mammogram is not available. Abdominal sonography and bone scan are required only if there are symptoms or signs suggestive of spread, or if alkaline phosphatase is elevated.

ER/PR/Her-2 testing done from biopsy (or after surgery from main tumor – for early stage), is important. Now these tests are more widely available, cost has significantly reduced, and reliability is good in major centers. Some patient assistance programs offer even free testing. These tests are useful in determining prognosis, and more importantly for use of several targeted therapies, which we will talk about later.

BREAST CANCER PART-6

This article presents approach to a breast lump and approach to a nonpalpable lesion seen only on mammography. Remember that 20% of palpable cancers are not seen on mammography.

Question: How to diagnose breast cancer? In other words, if there is a breast lump detected on examination, what should be the next step?
Answer: That assessment is based on examination and mammography/sonography. For a small lesion, where trucut(i.e. core) biopsy is not feasible, FNA (fine needle aspiration) is used. It is also helpful in lesions that are cystic on sonography.

If lump is high risk by either clinical or radiological criteria, FNA is generally not sufficient. Negative FNA does not rule out cancer, and positive FNA requires confirmation in most cases. Trucut biopsy is preferred, since it is least invasive, and yet provides enough tissue for complete diagnostic/prognostic tests. If not available, an incisional biopsy can be done, especially for lesions reaching skin. Excisional biopsy i.e. lumpectomy should be avoided in most cases. This is important to avoid need for two surgeries, since if positive, patients almost always need either a second larger lumpectomy by someone trained in cancer specific surgery or need a modified radical mastectomy and for axillary dissection.
Palpable lump with a normal mammogram needs equal attention. Remember that 20% of palpable cancerous lumps are not seen on mammography.

Que: What if breast lump is not palpable, but seen only on mammography?
Ans: Good question. These lesions are challenging since many of them are benign, hence over diagnosis with associated anxiety and invasive procedures need to be avoided. At the same time, this may be an opportunity to find very early cancer and improve results by many folds, at the same time reduce need for treatment such as chemotherapy.

Answer to this question is not always easy. American College of Radiology has set criteria for reporting of such lesions, to reduce under or over diagnosis. Based on the score, lesion is designated as e.g. low risk which should be followed with routine monitoring frequency. For some other scoring category, decision may be to repeat mammogram in 6 months, and keep close clinical monitoring. And for high risk lesions, immediate biopsy is recommended.

Since one cannot palpate early lesions seen on mammography, it is not possible to take an FNA or core biopsy of these lesions. There are special techniques to take a biopsy, such as needle localization biopsy. If such a facility is not available, a lumpectomy may be required. More invasive options are not preferred, since some of the lesions are benign, and a large number are precancerous (carcinoma in situ), which require a different approach.

BREAST CANCER PART-5

This article highlights strategies for prevention of breast cancer in women who are high risk, and the fact that there are no blood tests for diagnosis of breast cancer.

Que: What is the role of tumor markers in early diagnosis of breast cancer?
Ans: It would be nice to have a simple blood test to make diagnosis. However, at present there is NO one blood test or a series of blood tests that can definitively establish diagnosis of breast cancer or rule out such a diagnosis if negative. These tests e.g. CEA or CA 15-3 have a limited but useful role in the follow up of some patients whose cancer has spread. This question is important since often patients get a profile of blood test when they feel a breast lump. When they find that all tests are normal, they consider that they cannot have a serious illness like cancer, and do not go for further evaluation.

Que: Now Dr Shah, what can a “High Risk” woman do to Prevent Breast Cancer?
Ans: “High Risk” women are as defined in last part. Approach is individualized and a detailed counseling is necessary. Since options include radical surgical options, and few medical therapies, a complete discussion of pros and cons is important. Note that diagnosis of BRCA1/2 mutation is available in India, with a simple blood test, although expensive at this time.

Following options are available to reduce risk of breast cancer.
Mastectomy – Bilateral Radical: reduces risk by more than 90%. The psychological impact needs discussion. Women with extreme fear of breast cancer prefer this option, however. Mastectomy can be followed by immediate or delayed breast reconstruction plastic surgery, reducing psychological impact.
Salpingo Oophorectomy – Bilateral: after child bearing. Reduces risk of breast ca by over 50%. It is also recommended in patients with BRCA1/2 as they have a high risk of ovary/fallopian tube cancer as well, and there are no good tests to diagnose ovary ca at an early stage.
Tamoxifen – an oral hormonal agent, for 5 years. In women defined as High-Risk in last article, as well as in women with moderate risk defined by score on GAIL model, women with atypical hyperplasia in breast biopsy. Benefit in High-Risk women, especially with genetic abnormality, is not well defined and hence surgical options are preferred. Reduces risk of breast ca by about 40%. Long term benefit i.e. after 7 years, is not known. Tamoxifen has small but significant risk of deep vein thrombosis/pulmonary embolism, uterine cancer. This is important as drug here is being used in otherwise healthy women.

BREAST CANCER PART-4

This article highlights what can we do to Prevent breast cancer, in HIGH RISK women.

Question: Now Dr Shah, what can a woman do to Prevent Breast Cancer?
Answer: First of all we need to realize that not all women are at high risk. So the interventions need to be tailored to risk. For some high risk women, very aggressive approach may be required to save life.
Assessment is based on number of risk factors present e.g. any one of the following makes a woman “High Risk”:
known genetic mutation, such as BRCA 1 or 2, p53, PTEN
more than 2 first degree relatives with breast or ovary cancer
lobular carcinoma in situ
history of thoracic irradiation at a very young age
Rest of the women are assessed with a tool called “modified GAIL model”. It is not meant for Indian women, but can serve as an approximate guide.

Que: So you are suggesting that most women are not high risk. Is it safe to assume that they can follow only lifestyle changes?
Ans: NO, lifestyle changes are not enough. Since breast cancer rates are fairly high in Indian women, and seem to be rising, we need to use other measures. These tests are called Screening Tests. These are shown in western studies to be effective in detecting cancer at an early stage, and save life. They include:
Mammogram: a special type of x-ray of breast – every one to two years
Breast examination by a doctor – every year – any doctor can learn this. In the West, it is performed by most doctors, including general practioners.
Breast examination by woman herself – every month
These tests should start after age 50. Some people recommend after age 40. Remember that none of these tests are full proof. Hence one should use them in combination. Screening should be started after discussing its advantages and disadvantages, as it may not be suitable for everyone, especially since there is little data for Indian population.

Que: What exactly is a Mammogram ? Is it easily available ?
Ans: Mammogram is a type of x-ray and requires a special machine. Very few facilities exist for this however the number is rising. Technically it is one of the most challenging studies to read and interpret properly. There are many false positives and false negatives. If woman has a lump in breast, but mammogram is normal, she should still be evaluated, and if required biopsy should be done.

Also, mammogram is of very little or no value in young women with dense breasts, usually below age 40. In this age group, it can be very misleading and is NOT recommended.

Most radiologists combine sonography with mammography to better evaluate any suspicious areas. Sonography is not recommended as a screening tool by itself. MRI with a special coil has recently been found to be useful as screening tool.

BREAST CANCER PART-3

This article highlights what can we do to Prevent breast cancer.

Que: Now, Dr. Chiragbhai, can you tell us what should the majority of women do?
Ans: Modifiable risk factors that we saw last time are in our control, and we must try to reduce them. They are also good for overall health and reduce risk of heart problems, stroke, diabetes, arthritis, and many other cancers as well. These include:
Alcohol – avoid alcohol. Women seem to be more vulnerable to risks of alcohol and even one to two drinks per day increases risk substantially.

Exercise – regular exercise is clearly shown to reduce risk of breast cancer. Most middle class and up people in India have a vehicle, and very few exercise daily. Hard chores of home are generally done by maids in most households.

Diet – low in fat, and high in fruits, vegetables and grains seems to reduce risk. It is important to note that increasing intake of fruits and other components is essential and not just reducing fat. Various low fat diet options are available, and they should not take place of natural foods such as fruits, vegetables and grains. In short, traditional Indian diet of grains and vegetables, with addition of fruits is what we need to follow. Reduce sweets and fried foods. Many of our homes have fried foods as snacks. Consider adding more fruits to snack time. Ghee has not been evaluated in Western studies, which is likely different compared to oil and butter. It is prudent, however, to use everything in moderation.

Weight – obesity is an independent risk factor, and one that can be controlled with early institution of lifestyle changes noted above. Once established, it is comparatively difficult, but not impossible to lose weight. Marked weight gain after age 18 (over 25 kg), type not uncommonly seen in urban Indian women especially after childbirth, is also an important avoidable risk factor.

It is important to remember that earlier we establish a healthier lifestyle, more are the benefits. Since tissue development occurs early in life i.e. before youth, majority of the risk also likely gets established earlier in life. There is some evidence to suggest this theory, from various studies. One example is that of tobacco use, which if started at an early age, needs less number of years to result in mouth cancer or heart attack in case of smoking. This issue is very important, as more of our children and teenage are now adopting western life style, such as increasing obesity, high fat diets, sedentary life and others.

BREAST CANCER PART-2

This article emphasizes various risk factors – modifiable and non-modifiable.

Question: Now Dr Shah, what leads to breast cancer, what are the risk factors ?
Answer: There is a large body of literature on this subject with many very large scale studies. This has been summarized well on the website nccn.org for the interested readers. We don’t know the reason in all cases.

Que: What are the known risk factors ?
Ans: We like to divide them as non-modifiable and potentially modifiable.
Non-modifiable risk factors are:
Family history: breast cancer in a first degree relative is a significant risk factor. More the number of relatives and Younger the age at diagnosis, higher the risk.
Genetics: many of the patients with strong family history have an underlying identifiable genetic mutation such as BRCA1 or 2 mutation, that can be tested for to identify family members at risk. Not all family members obtain this mutation from their forefathers.
Female gender: a very small proportion of breast cancer is seen in men.
Age: increasing age is associated with increasing risk, especially after age 50, and it continues to increase with advancing age.
Early Menarche (before 11) and Late Menopause (after 55) – both increase risk, as they likely increase exposure to estrogen. This risk factor is potentially a result of lifestyle changes, but not clearly proven.

Que: What are the potentially modifiable risk factors ? I think our readers are more interested in knowing about them.
Ans: Yes, and that is where biggest impact is possible in preventive efforts. Following numbers give an idea of what we can achieve as a country if we control these risk factors. Incidence in USA is over 200,000 new breast cancers per year, with a population of about 240 million, whereas in India it is still only about 80,000 per year with a population of about 1000 million. This is due mainly to the difference in lifestyle. In other words, if we adopt all the risk factors similar to USA population, our incidence of breast cancer could potentially become 800,000 i.e.10 times the number what we have today. Unfortunately however, we are changing fast in the wrong direction.
Obesity – high weight especially significant weight gain at a young age, or after menopause is an important risk factor
Alcohol consumption – one to two drinks per day significantly increase risk.
Nulliparity – not having children, or having less number of children.
Older age at first live birth.
Current or prior estrogen and progesterone hormone replacement therapy – especially if long term i.e. many years.
Personal history of benign proliferative disease of breast – having a normal breast biopsy in past without atypical hyperplasia does not seem to increase risk.

The so called Western lifestyle seems to increase risk. Study of Japanese women have shown that after they moved to USA, their risk increased, which is likely lifestyle related. This is especially important since obesity and sedentary lifestyle are fast increasing in India, and more so in Gujarat.

BREAST CANCER PART-1

This article highlights that incidence of Breast Cancer is high in India, with over 200 women being diagnosed every day, and rates are rising, but there is optimism with tools for early diagnosis and better treatments.

Question: Why are you starting oncology educational series with breast cancer?
Answer: Breast cancer is one of the most common malignancies world wide and now in India as well. Over 80,000 women get a diagnosis of breast cancer every year i.e. over 200 women per day are diagnosed with a new breast cancer. That is a very high number. Even more concerning is the fact that with adoption of western lifestyle, incidence in India is rising, that too among more and more younger women. This appears similar to the marked rise in incidence of heart disease and diabetes in India, more so in Gujarat. Earlier we thought that these diseases also occur mainly in the West, and not here.

Que: But is there any major change in what we can do about breast cancer?
Ans: Oh! Yes, of course. Today it is one of the most curable malignancies. In the western world, there are many survivors now, including many famous people who have then helped to generate awareness, latest name being the famous pop star Kylie Minogue. There are large organizations now focusing specifically on issues of cancer survivors, such as American Society of Clinical Oncology. The fear has now been replaced by Optimism. There is a conscious effort to spread awareness about both Prevention/Early Diagnosis and Availability of Many Treatment Options for all stages of breast cancer. The change is attitude towards a new diagnosis of breast cancer in the west is comparable to our change in attitude now towards a new diagnosis of heart attack or that of advice for a coronary bypass surgery. We do not fear the later but rather discuss treatment options with our doctors and take a decision.

Que: You seem very optimistic about Breast Cancer. What do you think are the reasons behind this change in attitude?
Ans: It is a combination of both major scientific advances and what I call “social will”. Social will is the society’s desire to change outcome, to improve well being. It is very important because it gears up everyone including the common man, doctors and other health care providers, patients and relatives, academia, media, industry, NGOs, and politicians, and all the stake holders. This Social Will makes everyone work towards the common goal. This is what led to major reductions in mortality from infectious diseases e.g. use of sanitation/clean water/mosquito control coupled with availability of antibiotics/antimalarials/AntiTB drugs/vaccines. Drugs alone are clearly not sufficient.

What is most exciting to me as an oncologist however are the scientific advances which have improved all aspects of Breast Cancer Care, and are going through significant changes every few months: Knowledge of Risk Factors and biology leading to better Prevention, Early Diagnosis and better Prognostication, Tailor made therapy for individual patients, newer methods of Surgery/Radiation and Drugs leading to better CURE rates/less side effects/better functional outcomes, better tests to assess response to therapy. Some of the advances have actually reduced the cost of treatment by reducing need for hospitalization, less radical treatments, less complications. What is more, with use of IT, there are many tools that help us and patients to choose the right treatment and understand impact of treatment. There are very large scale clinical trials which have answered many of key clinical questions definitively and other questions are being answered in ongoing trials. Kind of cooperation among oncologists seen today was never before. Breast cancer is at the forefront of medical advances, among all cancers.

Que: What are the Aims of this series?
Ans: Aim is to bring about similar change in attitude towards cancer, generate the Social Will to change outcome/to improve well being of society as a whole, and to spread awareness about the existing scientific data. Hopefully this will also result in more research relevant to Indian scenario. Doctors and other health care providers should be at the forefront of bringing this change, through knowledge and their social stature. India is soon becoming an economic superpower, and our duty is to take care of nation’s health to sustain this growth.