April & May 2015 Surgery Sisters

Audrey, hope your first day back at work is a good one. What was up with your left hip on the bone density scan?

mdoc524, yahoo on getting rid of the drains!! Very frustrating about the lack of communication re bra requirements and a waste of money on tank tops you didn't need. All the PSs have different requirements and preferences. I'm still wearing my light compression bra at night. I'm at 7 wks now, and no longer need to wear it, but It is so comfortable and I am going to wear it at night until 8 wks. I purchased it myself, as my PS said it was a lot better than what she would have provided.

SuzyQ42, I don't know what you do other than diving, but if you do a lot of activities and sports, you may want to do a pros and cons list of TRAM vs implants (or DIEP/perforator flap, if you have enough fat). Your personal situation and preferences will help you decide the right decision for you. Personally, I am way too active to sacrifice muscle and I have no fat, so flaps weren't an option. The plus side of flaps is they feel nicer and you won't need to have them replaced in the future, but you have the donor site scar(s), longer surgery and recovery. Whatever your decision, get the consolation boobs you want. I am really happy with my implants. They look a tad fake on my lean frame, but I don't care and DH has given them two thumbs up. My PS did an amazing job and they are bang on symmetrical and the nipples are perfectly placed. Damn, she's good. One and done...I won't need a revision surgery. It's important that you like your doc, so that's great you do. Did you go BC shopping yet?

Jackbirdie, hope you are feeling better and getting stronger everyday and please weigh the risks/benefits of #6. I am worried about you and am concerned that proceeding could cause permanent detrimental effects and damage. Obviously your decision, but remember you are in the bonus round. Many pages back you said I should take PMR53's wise advise and I did...now I'm throwing that right back at ya, and you should consider what she suggested a couple of pages back re risk/benefit. As you yourself have said, you will get the biggest benefit from hormonal therapy. What's your E+% ? BTW, the kittie is cute, but I'm a dog person and allergic to cats. Where's my Jack? Both together would be perfectly acceptable.

Sisters, if exercise hasn't been a part of your life before, I encourage you to adopt it, to the extent that you are able during tx. It will minimize your SEs, release endorphins and help you feel better, reduce inflammation, help your body function better, recover faster and make you feel better about yourself. I am extremely active and my fitness has played a big role in my speedy surgical recovery. I will write an update post tomorrow on my recovery, as I don't have time today. While I do a lot of high intensity exercise, I love yoga. Yoga is great for flexibility, core strength, relaxation. stress relief and calming your body. Livestrong has a 12 week program at many YMCAs in the US targeted for cancer patients that is free. Toronto has Gilda's Place and Toronto Rehab Institute. Hamilton/Burlington have the CanWell program (developed by McMaster University and Hamilton Health Sciences), which will be rolled out at other YMCAs in Canada. Those are the free programs, but if you are willing to pay, there will be all kinds in your area, but you will have to modify accordingly for yourself, or speak to the yoga teacher. The free programs are tailored to cancer patients and the instructors should be knowledgeable about range of motion limitations and lymphedema. Check your community to see if there are any yoga programs with instructors trained to teach cancer patients.

Healing wishes and hugs to all my sisters in your recoveries. Be the best that you can be. Some of the other sisters will come along and tell you to be kind to yourself, which you should. I want you to push yourself a little out of your comfort range. Try something new. You are going to feel it using new muscles. There's good pain and bad pain. If it hurts, stop, but using muscles in new ways will stretch them and you will feel it over following couple of days. Start easy with walking and then if you are up to it, try additional activities, like cycling, yoga, Zumba - whatever appeals to you. Embrace fitness. Peace be with you. Namaste. (Translation: I honour the light/spirit in each of you).

Jackbirdie, this is a topic that warrants further research. More to come. Thanks for the photos. All three of you together resting peacefully is so nice. This will be a work in progress and I will edit this post, so that all the info is in one place. I will add some sources at the final stage.

CYP2D6 exists in multiple genetic forms and can be classified according to one of four levels of activity: poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The EM phenotype is expressed by the majority of the population and is therefore considered the norm. PMs inherit two deficient CYP2D6 alleles and, as a result, metabolize drugs at a notably slower rate. This leads to an accumulation of high levels of unmetabolized drugs that are CYP2D6 substrates, such as Tamoxifen, a greater potential for adverse events and drug–drug interactions, and lower efficacy for drugs requiring CYP2D6 activation.

More than 100 CYP2D6 variant alleles have been identified as of 2014. An allele is any one of two or more variations in a gene that occupy the same location on a chromosome. CYP2D6 is on chromosome 22. Four of the most prevalent alleles, CYP2D6*3, *4, *5, and *6, account for 93% to 97% of PMs. CYP2D6*4, the most common variant (~25% frequency in whites), causes a splicing defect. CYP2D6*3 (2.7% frequency) causes a frameshift mutation, and CYP3D6*5 (2.6%) is an entire deletion of the CYP2D6 gene. Individuals homozygous for these alleles have no CYP2D6 activity.

Activity status of CYP2D6 alleles (the most clinically significant are in red):

The impact of CYP2D6 activity differs on a drug-by-drug basis, depending on whether CYP2D6 is involved in the activation or inactivation of the drug. When CYP2D6 activates the pro-drug, as with the conversion of codeine to morphine, UMs may experience exaggerated pharmacological response, whereas IMs and PMs may experience muted effects. The opposite clinical effects would be expected for drugs deactivated by CYP2D6 — that is, drugs deactivated by CYP2D6 may show attenuated effects in UMs and exaggerated pharmacological response or toxicity in PMs.

CYP2D6 is the main enzyme involved in converting tamoxifen into its most potent anti-estrogenic metabolites, endoxifen and 4-hydroxytamoxifen. High plasma levels of endoxifen require the presence of fully functional CYP2D6 alleles. In poor metabolizers, endoxifen levels are decreased.

Tamoxifen is a pro-drug that is metabolized in the liver to active metabolites. Tamoxifen is metabolized by numerous cytochrome P450 (CYP) drug metabolizing enzymes including CYP2D6, CYP2C9, CYP2C19, CYP2B6, CYP3A4, and CYP3A5. The metabolites 4-hydroxytamoxifen and 4-hydroxy-N-desmethyltamoxifen (endoxifen) are thought to be mainly responsible for the clinical effects of tamoxifen. Both of these metabolites have about a 100-fold higher affinity for the ER compared to tamoxifen, but endoxifen is thought to be the major metabolite because plasma levels of endoxifen tend to be several-fold higher than that of 4-hydroxytamoxifen. Endoxifen formation mainly occurs via the conversion of the inactive primary metabolite N-desmethyltamoxifen by CYP2D6.

The response to tamoxifen (clinical efficacy and side effects) varies widely between individuals; this may be partly caused by differences in metabolism because of variations in genes such as CYP2D6.

Genetic testing

Genetic testing is available for many (~30) of the variant CYP2D6 alleles. Usually a patient's result is reported as a diplotype, such as CYP2D6 *1/*1. A result for copy number is also important when interpreting results for this gene. If the test results include an interpretation of the patient's predicted metabolizer phenotype, this should be confirmed by checking the diplotype and assigning an activity score to each allele (e.g., 0 for nonfunctional, 0.5 for reduced function, and 1 for each copy of a functional allele). The phenotype is defined by the sum of the two scores (e.g., poor metabolizers have an activity score of 0.

Significant interethnic differences in CYP2D6 allele frequencies exist. 5-10% of Caucasians are PMs (higher in Northern Europe and their descendants; one study had 4% for North American Caucasians; I need more data for a consensus), while <1% of Asians are. More on other ethnic variations to come.

Jackbirdie, evidence is inconclusive for routine testing. I need to investigate further and will report back. I am undecided at this point in time whether I will request it for myself. For you, I think it would be prudent to discuss with your MO having the test. Drug-drug interactions and efficacy of Tamoxifen would be impacted by your CYP2D6 status. You may be taking multiple drugs that are metabolized by CYP2D6 (narcotics and psychotherapy drugs amongst others - see list below) and the info would help your MO to avoid adverse drug–drug interactions and to better individualize your treatment with dose adjustments or change of drugs. You could consider genotype testing for the most common non-functional alleles, CYP2D6*3, *4, *5, and *6, at a minimum, which account for the majority of PMs and IMs. I think your MO could make a case for medical necessity to have Medicare cover the test. I saw a couple of labs offering this test that accept Medicare. How well you metabolize narcotics on the list (do they provide you relief) may help you and your MO gauge your CYP2D6 status.