Monday, November 29, 2010

Histologic Grade

Within the last decade, histologic grading has become widely accepted as a powerful indicator of prognosis in breast cancer. The majority of tumor grading systems currently employed for breast cancer combine nuclear grade, tubule formation and mitotic rate. In general, each element is given a score of 1 to 3 (1 being the best and 3 the worst) and the score of all three components are added together to give the "grade" (1-4).

Until recently, the most common grading systems used in the United States were the original Scarff-Bloom-Richardson (SBR) system as described above and the Black method which emphasizes nuclear grading and excludes consideration of tubules as a criteria (9). In Europe, the Elston-Ellis modification of the SBR grading system (Nottingham grading system) is preferred and is becoming increasingly popular in the US (7). This modification provides somewhat more objective criteria for the three component elements of grading and specifically addresses mitosis counting in a more rigorous fashion (4). For example hyperchromatic nuclei and apoptotic cells which are counted in the original SBR system are excluded in the Elston-Ellis modification and the area being assessed is specifically defined in square millimeters. These modifications have enhanced reproducibility of grading among pathologists and to a considerable extent have fostered acceptance of grading by clinicians (7,10-20). An excellent historical discussion of grading systems can be found in Elston and Ellis (17).

Criteria for grading are an active area of investigation particularly in regards to defining more objective criteria for assessing nuclear grade and we should expect image analysis to greatly contribute to this area in the future. The beginner is encouraged to consult their local pathologist to determine which system is used in their institution. The examples provided here, by Dr. Hanne Jensen, illustrate how the Nottingham Grading System can be used to grade a tumor.

When, on my pathology report, I read "modified Bloom-Richardson Histologic Grade" -- I wonder if this is the Nottingham Modification.

I will ask!

Saturday, November 27, 2010

Retraction

Patients who received a local radiation boost to the primary tumor bed site had statistically significantly less retraction than those who did not receive a boost. Patients who had an extensive primary tumor resection had statistically significantly more retraction than those who underwent a more limited resection...

...All 6 patients who received 6000 rad by external beam had significant retraction and fibrosis while patients who received 5000 rad rarely showed significant changes. Local boost doses by interstitial implantation did not diminish the cosmetic outcome.

Thursday, November 25, 2010

Quizzes!

I love quizzes. I have books of odd quizzes -- psychology, personality --

These are cool cancer quizzes, the results have bar charts! And they are for all different kinds of cancer.

https://www.cancerprofiler.nexcura.com

Wednesday, November 24, 2010

Free Radicals!

Actually, we don't want to free them. So terminology aside....

There has been growing medical evidence that when excessive "free radicals" are allowed to exist near the nucleus of the cell, significant damage to the DNA of the cell results. This "free radical" damage may then lead to mutation of the DNA of the cell. When the cell replicates, this mutation to the DNA is carried to the next generation of cells and the actual genetic damage that occurs can lead to abnormal growth of the cell.

Despite the "may", this is actually close to what does happen when cells turn into cancer cells: the genes are altered. The Oncotype DX tests 21 genes; the canadian algorhithm, 50. I'm going to look up the Seatlle computer model too.

Well, it is not what we're interested. Here's the title of his '96 paper:

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

We're not very interested in metastatic cancer here. And not very interested in 14-year-old research. Let hope it stays that way!

The free radicals, though, changing genes -- this does seem to be an idea with merit and proof. Medical doctors want to be able to identify the change to be able to treat; nutritionists leave on a countering free radical agency tangent.

At the heart of most of this is one of my questions for my allergist/immunologist and my oncologist: in younger people with low-grade, low-stage tumors fully removed, and/or people with compromised gastrointestinal systems and immune systems, is it wise to depress the immune system in order to let the chemo deconstruct the cells more efficiently, or is it better to keep immune function up and at-risk systems protected to prevent permanent damage -- when the side effects *could* outweigh the small risk of -- not recurrent cancer (tho that risk is quite small), but recurrent, metastasized cancer (that risk is even smaller)?

Tuesday, November 23, 2010

need to set up a link list; not working this am
http://www.bccancer.bc.ca/HPI/DrugDatabase/DrugIndexPro/default.htm
Other chemotherapy drugs commonly used for treating women with breast cancer include docetaxel (Taxotere), vinorelbine (Navelbine), and gemcitabine (Gemzar), and capecitabine (Xeloda).
cyclophosphamide, epirubicin, and fluorouracil

Epirubicin is an anthracycline drug used for chemotherapy.

Similarly to other anthracyclines, epirubicin acts by inhibiting DNA and RNA synthesis. It also triggers DNA cleavage by topoisomerase II, resulting in mechanisms that lead to cell death. Binding to cell membranes and plasma proteins may be involved in the compound's cytotoxic effects. Epirubicin also generates free radicals that cause cell and DNA damage.

The most serious side effect is heart damage.
doxorubicin (Adriamycin), followed by CMF
doxorubicin (Adriamycin) and cyclophosphamide with paclitaxel (Taxol)

AC

doxorubicin (Adriamycin) and cyclophosphamide (this therapy is called AC)

CAF

cyclophosphamide, doxorubicin (Adriamycin), and fluorouracil (this therapy is called CAF)

CMF

cyclophosphamide (Cytoxan), methotrexate (Amethopterin, Mexate, Folex), and fluorouracil (Fluorouracil, 5-Fu, Adrucil) (this therapy is called CMF)

The cytoxan disrupts menstruation; some doctors suspect that the benefit from chemo for younger women is merely this.

Rare, but only the young

Brachial nerves -- from the lower neck and upper chest -- become irritated or damaged, causing mild discomfort in the shoulder and arm.

Factors that MAY increase the risk of developing brachial plexopathy include a higher dose of radiation, a larger treatment area, young age, and CMF chemotherapy (cyclophosphamide, methotrexate, 5-FU) given at the same time as radiation.

Other symptoms include numbness, tingling, or burning sensation as well as weakness of the arm and hand. Brachial plexopathy is rare.

About that Arm

The condition can develop at any time (after surgery). That's about 40-50 years! It is a chronic, lifelong condition that may worsen over time if left untreated.

All breast cancer patients who have had an axillary lymph node dissection should avoid injury or infection in the affected arm: sunburn, heavy lifting (I've been told more than 30 lbs unassisted from other arm), constriction or blood drawing, or infection of the affected arm or hand.

Effective treatments include specialized massage (complete decongestive physiotherapy) and elastic pressure sleeves. << these DO work, btw

Monday, November 22, 2010

Bone Scan, Bone Marrow

this is where growth factors come in -- I don't know how -- and of course, bones make blood...

Fatigue

I have a friend who has recovered from CFS, although she does not have the stamina I know she wants. So I think of her when I see "fatigue." That is, I know there is a substantive difference between being shagged out after a long squalk and suffering from exhaustion and fatigue. What these differences are, tho, dunno.

For the majority of patients, it is only a temporary condition that resolves over time when treatment is completed; but for others it may be chronic (meaning it doesn't go away).

The cause of fatigue is poorly understood but contributing factors may include anemia, sleep disturbances, depression, the disease itself or the treatment(s).

Here we go! Anemia: pretty straightforward -- you're anemic or not. Can you get iron shots? Supplements? or not?

Sleep disturbances. This is not about car alarms go off at 4 am nor about a wretched night with two hours -- which happens to everyone. What it is precisely, I'm not sure.

Depression. OK. This will eventually be another topic. But for now: depression the side effect is different from garden variety depression, chemical imbalance, situational depression and exhaustion. If my experience with the birth control pill for abdominal pain / ovarian cysts leading to clinical depression is any indicator, depression brought on by radiation therapy is the real depression, difficult to explain while you're suffering from it that no you're not actually depressed like "hey, life sucks and then you die, oops, I have cancer, spiral, sucking noise," but "40 ton monty python weight falls on head after being zapped by a huge machine" depression.

more cut n' paste I will digest later:

Patients may feel weak and dizzy with a desire for rest and sleep. Other symptoms include pain in the legs, or difficulty climbing stairs, walking short distances, or being short of breath after only light activity, like cooking a meal or taking a shower. Some patients report difficulty thinking, forgetfulness, and an inability to concentrate.

There are no medical tests to measure fatigue. No one knows the exact cause of cancer-related fatigue, but causes are usually multiple. Any physical or emotional change can deplete energy. Varying levels of fatigue may be experienced, depending on the individual patient situation and cancer treatment(s).

Radiation Booster

First I'd heard of it!

A typical course of radiation therapy is five days a week (Monday through Friday) for six to seven weeks (usually 35 treatments) on an outpatient basis. Weekend rest breaks allow damaged normal cells to recover. The actual radiation is delivered over two to five minutes; however, each session can last 15 to 30 minutes because of the time required to set up the equipment and position the patient correctly. During this time, the patient receives small amounts of radiation daily to the entire breast and, if necessary, the axillary (underarm) lymph nodes and lymph nodes above the collarbone. Radiation to lymph node areas associated with the breast is usually unnecessary if the lymph nodes are negative. Patients with positive lymph nodes (underarm, above the collar bone, or beneath the breast bone) may or may not need radiation to these lymph node areas, depending on the patient situation and tumor characteristics.

Upon completion of the initial course of radiation, a final, smaller portion of radiation is usually given to the tumor bed (area where the tumor was removed). This final dose is called a "boost or booster dose." There are two methods to deliver booster treatments. The most common method is external delivery (like the initial course) and may last from one to two weeks.

Newer methods of delivering radiation boost are available and are referred to as partial breast irradiation (PBI). PBI targets the radiation to the area of the breast most likely to have a cancer recurrence, the site around the lumpectomy. Three types of PBI treatments are used most commonly:
Multi-catheter brachytherapy (also known as "interstitial brachytherapy")
Balloon catheter brachytherapy (MammoSite® Radiation Therapy System)
Three-dimensional conformal external beam radiation therapy
These methods are all effective and allow the radiation oncologist to deliver a higher total dose of radiation to the area where the tumor was removed.

the vax

A novel new cancer treatment that is being tested in scientific clinical trials such as gene therapy (drugs designed to replace defective genes with normal ones), antiangiogenic therapy (drugs that block the formation of new blood vessels that feed the tumor) or tumor vaccine therapy.

her negative and immunotherapy confusion

Biological therapy (also known as immunotherapy, biotherapy, or biological response modifier-BRM-therapy) uses biological agents (drugs) to stimulate, enhance, modify, repair, or manipulate the immune system to fight infection, cancer, or other diseases.

One type of biologic therapy that has evolved in breast cancer is monoclonal antibody therapy. Monoclonal antibody therapy is a type of biologic therapy that has been found to be effective in fighting certain types of cancer. Antibodies are proteins made by the body's own immune system that are directed against foreign and infectious agents, called antigens. Monoclonal antibodies are antibodies developed in a laboratory as medicines to provide specific anticancer action in humans. For example, the drug, Herceptin® (trastuzumab), is a monoclonal antibody used to treat breast cancer patients who are positive for the gene HER2.
Chemotherapy with a drug or drug combination other than anthracyclines (doxorubicin, epirubicin), taxanes (paclitaxel, docetaxel), or vinca alkaloids (vincristine, vinblastine, vinorelbine). Other chemotherapy drugs commonly used to treat breast cancer include:

methotrexate (Mexate®)
5-fluorouracil (5-FU) with or without leucovorin
mitomycin-C (Mutamycin®)
gemcitabine (Gemzar®), or
capecitabine (Xeloda®)
Chemotherapy for newly diagnosed breast cancer usually includes 2 to 3 drugs from different types or classifications of agents. Chemotherapy for recurrent breast cancer may also include several drugs from different classifications or may simply be a single drug depending on the individual circumstances, medical history, and doctor's evaluation and treatment decision.

taxanes, ooh, ooh, the taxanes...

Chemotherapy that includes a drug from the class of chemotherapy agents called taxanes (also referred to as antimicrotubule agents), which includes paclitaxel (Taxol®) and docetaxel (Taxotere®).

For example, a common taxane-based chemotherapy regimen available for breast cancer is AC (doxorubicin and cyclophosphamide) followed by paclitaxel (T).

Chemotherapy for newly diagnosed breast cancer usually includes 2 to 3 drugs from different types or classifications of agents. Chemotherapy for recurrent breast cancer may also include several drugs from different classifications or may simply be a single drug depending on the individual circumstances, medical history, and doctor's evaluation and treatment decision.

anthracyclines -- better not be anthrax!

Chemotherapy that includes a drug from the class of chemotherapy agents called anthracyclines, which includes doxorubicin (Adriamycin®), daunorubicin (Cerubidine®), epirubicin HCL (Ellence®), or mitoxantrone (Novantrone®--a drug very similar to the anthracyclines). These drugs interfere with cell growth.

A common example of an anthracycline-based chemotherapy regimen for breast cancer is CAF (cyclophosphamide, doxorubicin, 5-fluorouracil), CEF (cyclophosphamide, epirubicin, 5-fluorouracil), or AC (doxorubicin, cyclophosphamide).

Chemotherapy for newly diagnosed breast cancer usually includes 2 to 3 drugs from different types or classifications of agents. Chemotherapy for recurrent breast cancer may also include several drugs from different classifications or may simply be a single drug depending on the individual circumstances, medical history, and doctor's evaluation and treatment decision.

DCIS

I do have micro DCIS -- inoperable becos so small, and why would one grab them anyway -- on ducts in the breast with the tumor. This is related to having the fibrous/dense/lumpy sort of breasts.

What is a Tool

I mention this because wizards, data models, and other software "tools" -- which are tools by definition, but which aren't tools they way we think of them usually (as instruments or solutions) are 1) what oncologists use, 2) among the things I used to develop, 3) what is available now.

Such as

https://www.cancerprofiler.nexcura.com

I would like to demystify these, and I would LOOOVE to make one in exchange for the canadian algorhithm itself.

Novel Therapies

[expected joke about Tolstoy]

When I talk about immune therapy, I mean

Novel therapies - these treatments are also called "targeted therapies" because they target individual cancer cells and leave normal cells alone (unlike chemotherapy and radiation). Types of novel therapies include anti-angiogenesis therapy, which helps stop cancer cells from developing new blood vessels, and immunotherapy, which stimulates your own immune system to fight the cancer.

Steroids

Ah, yes. Well, we know about prednisone, but what else? Well, one thing is that they are often included in chemo to reduce side effects, but have similar side effects of their own.

I would prefer to reduce side effects through other means, mostly because right now, I feel the side effects that are important in my particular case to mitigate are destruction of my intestinal lining.

I am unconcerned about loss of appetite (which I have anyway -- has no one heard of ice cream? what is wrong with people? I know people who are on loss of appetite meds -- they don't want to eat, so they feel weak. Again: ice cream. Most of the people I know who suffer from loss of appetite / fatigue also eat non-fat, high fiber diets just for the heck of it. You go over for dinner and they've got a big bowl of spring greens with oil and vinegar dressing, 4 oz. of chicken or fish for each diner (aka rations), and some bread. HELLO???? how about meals you'd eat even if you weren't particularly hungry? I've got plenty of those...)

How about this: which is worse: ice cream, or STEROIDS?

Steroids reduce tumor swelling, but genx breast cancers this blog is about are completely excised with lumpectomy: tiny little things.

Right now, I'm assuming, too, that my immune system needs boosting, not supression.

Arimidex vs. Tamoxifen

Arimidex (generic name, anastrozole) was FDA approved in 1996 to treat advanced (metastatic) breast cancer patients who have not responded well to treatment with the drug, tamoxifen.

Since Tamoxifen is not something I will be taking ;{ it might make sense to look into this. I have a feeling that there's going to be an argument that node involvement -- even with clear CT, PET, and bone scans -- could fall somewhere between the "little cells" brokering of fear and metastasis.

However, since side effects are gastro, means that it is particularly hard on that system.

Taxol / Abraxane

Abraxane is similar to Taxol but is not required to be dissolved in a toxic solvent prior to administration.

This solvent can cause allergic reactions in some patients, and to counteract these reactions, patients are often treated with steroids and antihistamines. Patients receiving Abraxane do not need these treatments.

Canadians Need a Tech Writer / Developer / Project Manager -- Like Me

Maureen O'Connor of the National Research Council co-authored a recent study on predicting cancer recurrence. Her team examined public data on more than 1,000 patients' breast cancer histories. They knew which genes were being expressed abnormally and which patients got cancer again years later.

“The problem up until now is a statistical problem,” says O'Connor. “It becomes a statistical nightmare to go and find the most important genes in all of that data.”

O'Connor and her team created a computer program to filter the data and find the most telling genes. They made an algorithm — a set of computations — to predict for any new patient whether her cancer is likely to recur after surgery by looking at fewer than 50 relevant genes.

“Not all women need to get chemotherapy,” says O'Connor. “This could be a guide for those who don't really need the full treatment.”

O'Connor's team tested the algorithm with hundreds of patient histories and found that when the algorithm recommends against treatment, it's correct between 87 and 100 per cent of the time, depending on the sub-type of cancer.

This is the only responsible way to go, isn't it? Test the tumor. Don't trial and error the chemo.

Sunday, November 21, 2010

Lifestyle, Round 1

Received this link and some other info. from a great gen x stage 1 survivor, cancer free for five years:

http://www.mammalive.net/

The other info. is very important too, but here are my comments on this overwhelming site.

1) I gravitated towards the balance sheet. This is an unusual document where debunked health lore is combined with medical advice. From the risk factors:

Dental problems: mercury fillings, root
canals, chronic infection in extraction sites
Replace mercury fillings with ceramic,
remove root canal teeth, clear infections.

Being infection-free seems good; I got rid of my single mercury filling for cosmetic reasons years ago. "Remove root canal teeth" seems very gnomic.

Normalize biological terrain.

What IS a biological terrain? Perhaps the folks at Terrain know.

Vegetarian, no dairy fat in diet, use curcumin
and bromelain; consider Wobenzyme.

This seems very suspicious to me on several levels, although my dad wanted to start with curcumin for heart, and I hooked him up with some tumeric rather than cheapo yellow mustard, which he'd only use on keilbasa anyway.

Immune deficiency, allergies.

This is of course a "risk factor" for everything, but also a positive thing: allergic? Your body is fighting an antigen.

Underactive thyroid; iodine deficiency.

These don't follow. Also, seaweed's not going to cure Graves Disease. I did find one seaweed that's sort of like squid ink noodles.

Alcohol increases risk.

There's info that says that if you're a total souse drinking more than a liter or two of of hard alcohol a week (if female = size), the risk outweighs the benefits.

Commercial hair dyes.

No breast implants; have them removed. << no evidence if they are newer, except that you need better technicians to interpret breast imaging then.

Go braless or use looser cotton bra. Shouldn't matter.

Eat organic. << First of all, a lot of organic foods boosters trust that organic foods & whole foods are going to *repair* damage somehow. This is not true. Also, even if you are not allergic to the organic additives, toxic additives in foods do come in "organic."

Do parasite cleanse once or twice yearly
Do liver cleanse once or twice yearly
Do bowel cleanse once yearly; replace flora

All of these are total nonsense. Don't do anything weird to your body which will upset it. I feel like I'm saying don't douche. Don't douche. There, I've said it. Oh, and don't pick your nose in public, and keep your legs crossed, but not your eyes.

Avoid antibiotics. << unless you're sick and need them. Surely everyone knows that the whole sugar/alcohol/candida thing is pseudoscience?

Use skin-brushing. Hmmm. Skin brushing.

But here are the real wacky ones: don't be near electricity, especially when working or sleeping. Don't fly. Use natural fiber blankets. Don't use plastic. Don't heat up oils (like olive oil). Don't use a sewer system/regular toilet.

I love that. What about cholera. Isn't that a bad thing, cholera? Isn't indoor plumbing so cool? Doesn't it harsh your vibe to step in human poo in the street (happens all the time in LA, NY... *seeing* human poo in the street... maybe this is part of the risk factor of drinking alcohol? you might slip and fall in poo?)

STOP THE ITCH

How long has my skin been itchy? I'm not sure. It seems to me that since this summer, I keep looking for the Aveeno assortment and benedryl creams we used to have -- finding only calamine lotion, which seemed awfully messy for lazy me. So I bought Benedryl Gel -- 4 oz! before going to Costa Rica.

But, because Benedryl has something in it that I'll probably be reducing -- propylene glycol? I think that's the estrogen mimic in it -- I didn't use it until the NIGHT OF THE CALVIN KLEIN WOOL NIGHTGOWN.

But now I'm itching like crazy. How / why? Well, it is very interesting:

I had some lymph nodes removed.

A side effect of having lymph nodes out -- or swollen, or damaged, or -- is itching. All body, non-rashy, itch. Can you find this info? Unfortunately, only on the lymphoma pages. So I'm going to put some stuff here:

The estrogen system is: estrogen made; estrogen broken down by liver; broken-down estrogen removed from body by healthy intestinal tract.

The lymph system is: liver, tonsils, spleen, thymus, lungs, bone marrow. Symptoms of lymph problems: fever, night sweats, itchy skin.

DUH. This itch is not from the small scars healing (they are, but they don't itch). This itch is not (well, hopefully) Hodgkin's Disease or NHL. It is not dry skin/dry air from being in surgery or turning the heat on now it is cold outside. AND IT IS SUFFERED BY HUNDREDS OF PEOPLE WHO'VE HAD LYMPH NODE BIOPSIES. See? Cause - Effect. Sure, lymphodema might be a serious side effect I might have. But the minor one I have right now is that just by having a dozen or so nodes missing, I have an ITCH. THAT THIS IS A FAIRLY NORMAL THING TO EXPERIENCE IS NOWHERE TO BE FOUND. Well, here it is: when you go to the pharmacy to get more dressing for your lovely and attractive drain (like all the crappy drains around here, I had to basically "snake" this one to get it working, too!), get some REALLY STRONG anti-itch cream -- not the namby pamby stuff in cosmetics. AND FEEL NORMAL, not like you might have NHL (well, I am afflicted by national hockey league, but that's something else).

For me, going to the scary sites was interesting, though, because, as I mentioned, I had a teeny tumor (all gone!) and no one expected this lymph thing. But I did have mono TWICE as a child. I do have immune problems (severe allergies). Thewy have a tie to the environment, the environment I was in when I had mono twice. I had such severe tonsilitis/strep/scarlet fever until I was about 30 that they kept my tonsils IN, and my throat's been a bit sore since Friday -- nothing terrible, and again, no sign of infection, inflammation -- but another sign of a lymph system adjustment.

And how is lactic acid involved, exactly?

Saturday, November 20, 2010

SHINGLES????

Since you can get shingles when your immune system is low from chemo, and since a friend of mine has it and really suffers, I'm going to look into the vaccine.

I did. Now my surgeon's going to look into the vaccine. Basically, as a gen x person, I still belong to the group -- like boomers -- that went out to play with a friend who had chicken pox in order to get it; these pox buddies were more or less carefully chosen based on the severity of the pox and relative ages -- so I did have chicken pox, through Ann Lauterjung (sp? gosh -- she was one of my best friends --). So did my younger sister (later of course). My parents had it and ...

boredom sets in...

Lymphedema

No, I'm not a tennis champ. Actually, I was top seed junior varsity the one year I played, but the bitchy coach wouldn't even give me numerals. Nope, but I use my right arm -- as do, I daresay, the vast majority of us at this point -- for my livelihood. And I am accustomed to hauling around heavy stuff, like grey water for our lawn in the summer, and sheets of drywall, and stuff. Again -- part of my livelihood.

Any mention of the fact that anyone working on a computer needs not only full right arm use, but is also in danger of a vicious circle of repetitive motion disorder / nonmedical arthritis / lymphedema. Or put it this way: how am I supposed to work? Take out the trash? Water the plants, plant the garden, take out the trash?

OK, so, aside from the work you need to do to pay for this thing, what else triggers the swelling? Exercise, especially running (oh, but you're supposed to exercise and lose weight, right?) and weight lifting, flying on an airplane...

Typically, more of the information is about losing weight and getting shirts with big sleeves and this appearance hullaballoo than about the special sort of massage and special pressure bandages that might be able to protect your arm and lessen the edema.

Nutty Nutrition

The same books, papers, sites, etc. that totally minimize the side effects of radiation and chemotherapy also encourage micromanaging diet for trace chemicals. Huh?

Yes, chemical pesticides are not good. Do I use them on my yard? Yup. Do/did they contribute to the air and water pollution in Decatur, IL? Yes. But look: chemotherapy killing healthy cells, your body working to make new healthy cells, and to fight bad old cancer cells. You want to tell me that, in a book about breast cancer, that there are more inches devoted to pesticides in grains that animals consume before they are in turn consumed, than to MITIGATING THE SIDE EFFECTS OF CHEMOTHERAPY? That the radiation that makes you tired is also, of course, temporarily destroying your immune system, more so if your lymph nodes are irradiated as well?

This is just as bad as the focus devoted to the nonissues of reconstruction, hair loss.

Obvious, too, that they are all over the ball park with weight gain. You're at greater risk for all sorts of complications, and also for recurrence, if you are heavy. But the medicines -- if you don't carefully control them -- make you gain weight, Hmmm.

Chemotherapy Research Begins!

Breast cancer: Reducing the risk of unnecessary chemo

November 8, 2010

Published in Nature Communications, NRC researchers have developed a tool to determine which breast cancer patients have little risk of their disease recurring. The tool -- an algorithm that identifies "gene expression signatures" or biomarkers that can predict low risk tumors with 87-100 percent accuracy in different groups of patients -- has the potential to virtually eliminate unnecessary chemotherapy.

How is gene expression test different from Oncotype DX?

In future, the algorithm may also help pave the way toward personalized therapy for cancer patients. "On average, every cancer patient has 14-16 mutated genes," says Dr. Wang. "Based on their unique genetic signature, we hope to figure out which mutations to target to block the cancer process in each patient."

This type of algorhythmic thinking has more in common with my general approach than a lot of the brokering of fear about recurrence being worse than the original cancer.

Examples of chemotherapy combinations used to treat breast cancer include:

cyclophosphamide (Cytoxan), methotrexate (Amethopterin, Mexate, Folex), and fluorouracil (Fluorouracil, 5-Fu, Adrucil) (this therapy is called CMF)
cyclophosphamide, doxorubicin (Adriamycin), and fluorouracil (this therapy is called CAF)
doxorubicin (Adriamycin) and cyclophosphamide (this therapy is called AC)
doxorubicin (Adriamycin) and cyclophosphamide with paclitaxel (Taxol)
doxorubicin (Adriamycin), followed by CMF
cyclophosphamide, epirubicin (Ellence), and fluorouracil
(the brand name of the drug is shown in parenthesis)

Other chemotherapy drugs commonly used for treating women with breast cancer include docetaxel (Taxotere), vinorelbine (Navelbine), and gemcitabine (Gemzar), and capecitabine (Xeloda).

Wednesday, November 17, 2010

LRR: Local Recurrence

Which patients appropriate?

(young age is powerful risk factor for local recurrence; important limitation
of MammoSite device is that breast tissue must be greater than 3cm in
thickness where the device is placed and there must be at least 7-to-10
mm of distance between the MammoSite balloon and skin to prevent
skin injury and possible wound breakdown.)

Because local recurrence has minimal impact on survival, could we define
a patient group with a low enough risk that no XRT (i.e., hormone
therapy only) is necessary? (recent data for women >70 shows LRR 4%
without XRT and 1% with XRT)

Will the excellent 3-5 year results for each of these partial breast treatment
techniques hold up over time?

Lancet on Partial Breast Irradiation

As you may know, there is a new article from June 2010 in the Lancet about [pick an acronym] in the UC hospitals.

This is from an older one:

These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30·5% versus 35·9% (reduction 5·4%, SE 1·7, 2p=0·0002; overall mortality reduction 5·3%, SE 1·8, 2p=0·005).

...

Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large.

Radiation Therapy

For those without lymph node involvement, and those who want to leave radiation in the arsenal of tools available for treating unlikely recurrences, partial breast radiation therapy is now an option.

Whole breast radiation remains the "standard."

Here's what the radiation people have to say:

Results
The Task Force proposed three patient groups: (1) a “suitable” group, for whom APBI outside of a clinical trial is acceptable, (2) a “cautionary” group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an “unsuitable” group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety.

Conclusion
Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.

http://www.redjournal.org/article/S0360-3016(09)00313-7/abstract

Here's more info from the paper:

All patients considered for APBI should be candidates for breast-conserving therapy (no prior radiotherapy, no history of certain collagen vascular diseases, and not pregnant) and should be committed to long-term follow-up to evaluate for recurrence, second primary cancers, and treatment toxicity.

*this paper does NOT recommend partial breast radiation for anyone stage 1 under 50, and everyone over 60, although NO radiation is indicated for stage 1 women over 60!!!*

Here's some more info: To promote appropriate multidisciplinary cancer care, the Task Force strongly recommended that the decision to treat a patient with APBI should be made only after the patient's consultation with a radiation oncologist and review of the final pathology specimen.

Here's what Cedars Sinai has to say:

Mammosite Partial Breast Radiation Therapy (PBRT)

Mammosite is a type of partial breast radiation therapy (PRBT). It is an implant that uses a catheter to deliver high doses of radiation to a localized area to minimize the radiation effect on surrounding tissue such as the lungs and heart.

PRBT is not for everyone. In determining whether a patient is a candidate for the procedure, a physician will consider the size of the lump (<4 cm), how close it is to the skin, the size of the breast, and tumor size and characteristics.

PRBT may be a viable option for patients that plan to have a lumpectomy or other breast conserving surgery and patients who have already had radiation therapy.

PRBT requires five days of twice-daily treatments rather than the six weeks of Monday through Friday treatments required for standard radiation therapy.

PRBT is as effective in prevent breast cancer recurrence as whole breast radiation therapy.

http://www.cedars-sinai.edu/Patients/Programs-and-Services/Radiation-Therapy/Radiation-Technologies/Mammosite-Partial-Breast-Radiation-Therapy-PBRT.aspx

My radiologist reported that this info. is for the "most tested" group, which is postmenopausal women over 60, under 70. She says that the studies / conferences she's attended recently only have 5 years of data for women under 45, and that data only involves hundreds, not thousands, of people.

She also reported that while the machine her office currently has, the trilogy medical linear accelerator, is good, it is not as good for partial breast as another machine that is available elsewhere. I don't know the name of that machine -- but it is what she used previously.

BOOST THIS BREAST, PLEASE

Newer methods of delivering radiation boost are available and are referred to as partial breast irradiation (PBI). PBI targets the radiation to the area of the breast most likely to have a cancer recurrence, the site around the lumpectomy. Three types of PBI treatments are used most commonly:
Multi-catheter brachytherapy (also known as "interstitial brachytherapy")
Balloon catheter brachytherapy (MammoSite® Radiation Therapy System)
Three-dimensional conformal external beam radiation therapy
These methods are all effective and allow the radiation oncologist to deliver a higher total dose of radiation to the area where the tumor was removed.

Current phase III research studies are underway to determine if partial breast irradiation (PBI), which involves a shorter course of radiation over 4-5 days, can be just as effective (good cosmesis, no increase in breast tumor recurrence, and no decrease in overall survival) as the current standard of 35 treatments over six or seven weeks of external whole breast radiation.

Mammograms

I have had to emphasize, over and over, to so many people, these stats:

Specifically, the USPSTF recommendations suggest women aged 40 to 49 without risk factors can avoid yearly mammography screenings for breast cancer until age 50. The ACOG guidelines advise that women can begin receiving Pap tests to look for cervical cancer starting at age 21 and then be screened every other year until age 30, at which time women should receive the test every three years.

This is, of course, unless you find a lump.

The post-cancer recommendation is only once a year! So, by early 2011, I'll be looking at what you can do other than looking for lumps and the yearly mammogram (which you will have post-cancer at any age under 49 -- because you now have a "risk factor."

Risk factor is not a meaningless term, nor is it especially meaningful.

Risk: Facts and Figures

Risk factors for local recurrence after breastconserving treatment of early breast cancer have not previously been evaluated in settings where mammography has been a major pathway to diagnosis of both primary tumour and recurrences, or in patients treated surgically by a formal sector resection.

this is from 15 years ago, though, http://annonc.oxfordjournals.org/content/8/3/235.abstract

Low age, comedo and lobular cancers and mammographic appearance of the tumour as a stellate lesion with microcalcifications inside the lesion indicate an increased risk for local recurrence after sector resection in stage I tumours at five years.

1) increased from what?
2) 6/190 w/ radiation vs. 42/190 w/o. 3.1% risk of recurrence with radiation.

Patients >60 years of age without comedo or lobular cancers are at low risk for local recurrence at five years even without postoperative radiotherapy.

Premenopausal women are at higher risk of recurrence than postmenopausal women after lumpectomy + radiation (ONLY 10 years ago!): http://www.cancernetwork.com/display/article/10165/68988

But what are those risks:

"Fortin et al[5] reported a ... 10% [IBTR rate] for T1 or T2 tumors"

Lymphovascular Invasion—Lymphovascular invasion has been associated with an increased risk of IBTR in many [13,14,59,62,94] but not all [4,12,65] series.

A new genetic test (Oncotype DX) can help determine the likelihood of late recurrence (for example, recurrence in 5 or 10 years) in newly diagnosed patients whose breast cancer is stage I or II, node negative, estrogen receptor positive {went on to say, and tamoxifin, but I cut that out because I'm not going to take it, but the test seems like a good idea anyway -- I'm going to ask about it.

Doesn't mention stage, or "grade" -- just invasive, which can mean many things. However, since this seems about as bad as it can get, here it is:

"For patients treated initially for invasive breast cancer, 5 percent to 10 percent will be found to have distant metastases at the time of discovery of the breast recurrence. The same proportion will have recurrences that are too extensive to be operated on. These patients are rarely, if ever, cured. Five-year cure rates for patients with relapse after breast conservation therapy are approximately 60 percent to 75 percent if the relapse is confined to the breast and a mastectomy is then performed."

http://www.radiologyinfo.org/en/info.cfm?pg=breastcancer

Serious

I suppose I could file this under "Risk."

How serious is serious?

This is an important question. YES, cancer is serious. YES, I want to treat it seriously. So do you.

But "throw everything at it" is a bad idea. I resent having to live in a vacuum of information between initial and final diagnosis: it has put me in a "shoot first, ask questions later" position, which is equally absurd (although my surgeon will point out that the MRI, ultrasounds, and core biopsy were questions we asked about my teeny tumor).

Say you have endometriosis or other precancers and small cancers of the uterus, ovaries, cervix... does anyone seriously recommend chemical castration to avoid recurrence?

Say you are at high risk for breast cancer: this blog isn't for you.

But for those who, again, with these very treatable curable cancers, please consider ANY recommendations to remove healthy organs carefully. I will suggest that removing breasts and uterus and ovaries is like removing tonsils. Can't get tonsilitis, but more likely to get bronchitis or stomach flu, which are more serious. Won't the cancer grow elsewhere, then?

Why are only female body parts targeted?

These are serious questions, too.

Tamoxifen

This is going to be a tome, and if so, this will be a chapter *separate from* hormone therapy, including estrogen reduction / anti-estrogen, PROGESTERONE / anti-progesterone.

Internet Drug Index has this warning on Nolvadex, brand-name Tamoxifen.

WARNING

For Women with Ductal Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer: Serious and life-threatening events associated with NOLVADEX in the risk reduction setting (women at high risk for cancer and women with DCIS) include uterine malignancies, stroke and pulmonary embolism. Incidence rates for these events were estimated from the NSABP P-1 trial (see CLINICAL PHARMACOLOGY-Clinical Studies - Reduction in Breast Cancer Incidence In High Risk Women). Uterine malignancies consist of both endometrial adenocarcinoma (incidence rate per 1,000 women-years of 2.20 for NOLVADEX vs 0.71 for placebo) and uterine sarcoma (incidence rate per 1,000 women-years of 0.17 for NOLVADEX vs 0.4 for placebo)*. For stroke, the incidence rate per 1,000 women-years was 1.43 for NOLVADEX vs 1.00 for placebo**. For pulmonary embolism, the incidence rate per 1,000 women-years was 0.75 for NOLVADEX versus 0.25 for placebo**.
Some of the strokes, pulmonary emboli, and uterine malignancies were fatal.

Here's more from the Lancet:

Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed ...

For ER-positive disease only (common in cancers in premenopausal women), allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50—69, ≥70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0·00001 for recurrence, 2p=0·01 for breast cancer mortality) more effective than just 1—2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0—4 and 5—14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.

The big question is 31% of what. For example, if after radiation, the risk of recurrence is 2-10%, a 31% reduction is actually a reduction of 3%-to-.66% -- definitely outweighed by side effects, if you are in a serious side effect risk group.

Tuesday, November 16, 2010

Contrast

Just passing this on: if you are allergic to contrast, it is probably to the kind you drink (which in many -- not all, but many -- cases is optional) or to all of it.

If you are allergic to certain corn / soy / common fruit flavors used to flavor the contrast, ask it be made without the kool aid.

That iodine / shellfish allergies are involved is *reportedly* a tall tale.

And just as a note: if you are allergic to contrast, maybe like me you were so sick when you took it the first time it was difficult to say why you were barfing and letting loose all over the scanner and then had horrible abdominal pain / gas for two days, YOU PROBABLY ARE, but try to call and find out exactly the brand you had, and make sure it is put into your records.

Oh, and on another note: you know how they bring you five cups, whether you're 6'4" or 5'4"? Have you read how "up to 4 servings of contrast" are good? If you feel yourself rejecting the contrast after 3-ish of them, stop drinking it, and let them know you've done your best, end of story, and no you're not going to hold it and pretend to try. You've got PEOPLE to read. If you feel that your doctor(s) need the easiest-to-read CT scan to do their jobs, even if it makes you sick, GET NEW DOCTORS.

You have a little time -- not a whole lot, but a day or two -- yes.

Lumpectomy

Outpatient -- this Friday. MRI is clear.

Risk

To quote myself:

But one thing is: risk of developing a certain cancer is different from risk of developing any cancer is different from risk of cancer recurring in the same person is different from the risk of *that particular cancer" recurring.

What is risk? Well, as a former risk manager...

1) don't let honest questions about risk be demonised as "gambling" vs. "responsibility" or "security."

There's an idiom about weighing risk. An important question to answer is what are the risks being considered, and are they applicable?

You will be asked to compare risks between apples and oranges. For example, the best oncologist in the area recommends lumpectomy, 7 weeks of full breast radiation, 5 years of tamoxifen followed by a lifetime of AI inhibitors, and extreme diet and lifestyle changes, even for those who regularly exercise and are not overweight. Is any oncologist who recommends differently not "the best"? Is the course of treatment recommended NOT "the best"? For whom? In fact, there are two classes of risks here, those of the recommended course versus your particular case, and those of hiring / patronizing a medical professional.

Epidemiology: Why You Don't Care About Broad Trends Until You're Cured

Unfortunately, if you're reading this, you're in a small subgroup of breast cancer -- lets face it -- survivors. There are hardly ANY recommendations good for the majority which are good for you, PLUS hardly any of the options have been tested in clinical trials on your risk group.

More soon, but this is part of the reason breastcancer.org, cancer.org, and even the majority of Susan Love, Susan Komen, and ... etc. uselessness. Susan Love's site does have lots of geeky research! but the search engine for it is very 1992: it is impossible to data mine with it.

If you feel moved by the knowledge you acquire and the people you meet while getting cured, by all means get involved in altering broad, worldwide trends. But I personally am going to ignore them until I'm d/d free, because the stats are misleading in my case. For example, "we always use tamoxifen on hormone-receptive cancers" and "tamoxifen has little impact on recurrence and survivability in even hormone-receptive cancers in premenopausal women, and the long term effects -- at 40-50 years survival -- simply haven't been studied" and "hormone therapies have been used for 100 years" -- oh really? Before World War I they were routinely yanking out healthy ovaries? I need to represent myself first.

Estrogen

Although most people think of estrogen as a single entity, these hormones are actually three biochemically distinct molecules the body produces naturally—estrone (E1), estradiol (E2), and estriol (E3). These three estrogen molecules have different activities that make them more or less "estrogenic." The estrogenic activity often determines the mutagenic or carcinogenic potential of an estrogen.

Another nutrition site: http://www.chiro.org/nutrition/FULL/Estrogens_Two-Way_Street.shtml

More from this site, though, because it seems sort of informative:

These estrogens break down or are detoxified into estrogen metabolites—daughter compounds—called 2-hydroxyestrone, 4-hydroxyestrone, and 16-hydroxyestrone.

In premenopausal women, the ovaries produce the estrogen estradiol (E2), which converts into estrone (E1), both of which must eventually be broken down and excreted from the body. This breakdown occurs primarily in the liver, and the excreted metabolites flow out in the bile or urine.

Studies show that when 2-hydroxylation increases, the body resists cancer, and that when 2-hydroxylation decreases, cancer risk increases.

But, all of this is for postmenopausal women and it is about risk, not actual cancer.

Oh no, now it is starting in on epidemiology. 'Nother backbone post needed.

But one thing is: risk of developing a certain cancer is different from risk of developing any cancer is different from risk of cancer recurring in the same person is different from the risk of *that particular cancer" recurring.

Leaky Gut?

I do not believe that there is something called leaky gut -- that eating certain foods makes the intestine porous. Well, maybe some random dude in the UK has it.

But when I read something like this (of course, from a site named "moondancer" -- so one expects to read less trustworthy opinion and more new age fad stuff of the "do no harm" category):

Use acidophilus supplements. While the liver breaks down estrogen before sending it to the digestive tract for elimination, bacteria in the intestines can turn these breakdown products back into estrogen.

I want to know: can it be true?

Well, the liver does break down estrogen and other hormones LIKE PROGESTERONE. So tamoxifen, which damages the liver, sounds like a pretty bad plan, doesn't it? But what about this, that your liver was working hard, but unless you take probiotics, your intestines will undo all of that work?

Lifesource4life (http://www.lifesource4life.com/conditions/c-fibroids.htm) doesn't seem any more authoritative than moondancer, but:

The liver is responsible for breaking down estrogen (and other hormones) and secreting the metabolites into the large intestine for elimination. If the liver does not metabolize estrogen and its metabolites properly, then it is recycled throughout the body.

While the liver is the dominant player in estrogen metabolism, the flora or “friendly bacteria” in the large intestine are also important in estrogen metabolism. They prevent the reactivation and recycling of these unwanted estrogens. Conversely, “unfriendly bacteria” secrete an enzyme called beta-glucuronidase that causes estrogen to be recycled back through the body via the large intestine.

Reading wikipedia, I get very little I understand:

Beta-glucuronidases are members of the glycosidase family of enzymes that catalyze breakdown of complex carbohydrates.[2] Human β-glucuronidase is a type of glucuronidase (a member of glycosidase Family 2) that catalyzes hydrolysis of β-D-glucuronic acid residues from the non-reducing end of mucopolysaccharides (also referred to as glycosaminoglycans) such as heparan sulfate.[2][3][4] Human β-glucuronidase is located in the lysosome. [5] In the gut, brush border β-glucuronidase converts conjugated bilirubin to the unconjugated form for reabsorption. β-glucuronidase is also present in breast milk, and its action contributes to neonatal jaundice.

Except, hm, looks like it is supposed to be reabsorbed, is estrogen a complex carb? and look up lysosome.

Looking up jaundice, the fault is bilirubin.

But look, there's more:

The bacteria in the adult gut convert conjugated bilirubin to stercobilinogen which is then oxidized to stercobilin and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border β-glucuronidase and reabsorbed. This process of re-absorption is called enterohepatic circulation.

Look up enterohepatic circulation.

Second, the breast-milk of some women contains a metabolite of progesterone called 3-alpha-20-beta pregnanediol. This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid (UDPGA) glucuronyl transferase responsible for conjugation and subsequent excretion of bilirubin.

Hmmm. Here we have PROGESTERONE.

Phototherapy works through a process of isomerization that changes trans-bilirubin into the water-soluble cis-bilirubin isomer.

Hmmm. This might be why moondancer said something like get plenty of sun but with very high spf sunscreen.

Thus far... noooo yoghurt...

One rat of each pair received an intraduodenal infusion of rat bile plus breast-milk; the other rat received a similar amount of bile and milk plus the beta-glucuronidase inhibitor saccharolactone. Rats receiving saccharolactone excreted significantly less bilirubin in their bile, suggesting that inhibition of beta-glucuronidase decreased intestinal absorption of bilirubin.

But wait, bilirubin, estrogen. Huh?

Diet

I have very little flexibility with diet, although, when I consider what I may eat, most of those foods except the typical (red meat, dairy, alcohol) to warn everyone away from are in fact anti-oxidant, immune boosting...

But I mention this because the difference between premenopausal women's diet and postmenopausal women's diet seems not to have been studied, and once again, a diet which "can do no harm, and MAY help" attitude is widespread in people in the position to tell women how to eat.

"High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer."

This is nice. It is from a scientific journal, http://cebp.aacrjournals.org/content/10/1/25.full.

Doesn't match the headline, "Reducing Bioavailable Sex Hormones through a Comprehensive Change in Diet" does it? Why? None of these findings applies to more than half the population of women, those at LOW risk for breast cancer (even though they may have it, or precancer), and recurrence, and mortality WHO ARE STILL NATURALLY PRODUCING ESTROGEN. [I fear that one of the rushes to induce menopause may be to force premenopausal women into something resembling the postmenopausal population using healthy ovary removal and remarkably dangerous and ineffective tamoxifen. But that belongs under a different heading.]

Ah yes, diet.

Monday, November 15, 2010

Welcome!

This is a site with several purposes and a few slants. I guess this should go in the "about" part too.

Purposes
To hold my notes, particularly links and quotes taken from online research. While there are several non-public softwares for doing this, I like the access anywhere, even from a waiting room computer, aspect of a blog.

Also, this information isn't as easy to find as it should be, given that most breast cancer sites contain only "soft" information and epidemiology statistics, and very little hard information and statistics for 1) very premenopausal women (currently 30-45 -- Gen X), 2) early stage breast cancer (DCIS and invasive ductal Class I -- small tumor, no node involvement), 3) spot radiation, 4) skipping tamixofen -- not for fertility reasons, but for other reasons, 5) ER+/PR+ (estrogen AND progesterone respondent tumor).

I would also like to have a spot to consider, separately, the language of illness in women among women, and ways women are treated differently -- as a class -- from men by professionals. But here at the outset, the difference in language is striking, and Sontag in Illness as Metaphor, etc., did not cover this.