I thought I was crazy when I noticed a seasonality to bc metastases

[Lani]

but look here...(again, in mice and not her2 specific...but metastatic bc is often her2 + even when the original tumor was not...and bc in mice syngeneic experiments is usually due to MMTV as I understand it which produces her2+ bc in mice )

Breast Cancer Res Treat. 2007 Oct 14; [Epub ahead of print]
Seasonal modulation of post-resection breast cancer metastasis.

Oh EY, Wood PA, Du-Quiton J, Hrushesky WJ.
Medical Chronobiological Laboratory, Dorn Research Institute, WJB Dorn VA Medical Center, 6439 Garners Ferry Road, Columbia, SC, 29209, USA.
Background Human breast cancer incidence, histopathologic grade, invasiveness, and mortality risk vary significantly throughout each year. In order to better understand this seasonal cancer biology, we investigated the circannual pattern of post-resection breast cancer metastasis, under genetically and environmentally controlled conditions. Methods Over a span of 14 consecutive years, we conducted 22 similar experiments to investigate metastatic biology of breast cancer among 1,214 C3HeB/FeJ female mice. All mice were kept in temperature-controlled environment with 12 h light:12 h dark photoperiod, with food and water freely available, from birth until death. At 10-13 weeks of age, each mouse received 20,000 viable syngeneic mammary cancer cells subcutaneously and the tumor bearing leg was resected 10-12 days after tumor inoculation for potential cure. Once 10% of resected mice were found moribund, due to autopsy proven pulmonary metastases, all remaining mice were sacrificed and metastatic lung nodules were counted. Results The incidence of post-resection pulmonary metastasis was not randomly distributed throughout the year, but peaked prominently in Summer and Winter. Although tumor volume at resection was strongly associated with metastatic potential, a significantly higher probability of pulmonary metastasis was observed if surgery was performed in Summer and Winter, regardless of tumor volume at resection, compared to Spring and Fall. Conclusion These results support the likelihood that human breast cancer seasonality is real and of biological origin. There are implications of this cancer chronobiology for breast cancer prevention, screening, diagnosis, and treatment.
PMID: 17934872 [PubMed - as supplied by publisher]

[hutchibk]

My mastectomy was Dec. 9 - my torso mets (lungs, chest nodes, bone met in neck) have all been discovered in the summer. However, my brain mets were discovered in March.

Interesting article.

[Hopeful]

Lani,

In your opinion, is fundamental bc carcinogenisis also seasonal? Perhaps there is something to the circadian rhythms (i.e., some specific endocrine action) that occurs to "jump start" things?

Hopeful

[Lani]

clearly there is some "clock mechanism" as tumors tend to recur in peaks
a certain number of months after surgery (not after lumps discovered) and the certain number of months differs by tumor subtype, at least w her2neu
the initial peak occurs 24-36 months or so after surgery as I understand it.

Circadian rhythm research is not well funded and research on melatonin is not very advanced at present it seems....

[Mary Anne in TX]

Lani, is it 24 - 36 months or 22 to ?
I wish I had written down alll the signatures like I tell myself when I read them. Maybe thats another unanswerable question. ma

[Becky]

The largest rise in the recurrence peak is 18 to 22 months. It levels out then and begins a descent but that descent doesn't get low until about 39 months. It really levels out low at around 5 years (hence the "glorious" 5 yr mark). However, women who are highly ER/PR+ peak again around 6-7 yrs (I am not entirely sure if this includes those that are also Her2+ as well or the plain ole standard ER/PR+). This makes sense as in the past, Tamoxifen ends after 5 years but most women wouldn't start that until 3-6 months after surgery (maybe more before dense dose chemo) so from surgery, they would be 5.5 - almost 6 years out. If Tamoxifen was just keeping things in check, then it would start to grow. Since the plain ole is slower growing, it might take a year to detect mets. This is the premise of 5 yrs Tamoxifen then 5 years of Femara (which reduces those late recurrences which I have read are about 4% - small amount).

I was a September girl.

[Mary Anne in TX]

Thanks, Becky. I've wondered if the "rules" were the same whether you were E+ or E -. ma

[tousled1]

I was originally diagnosed October 2005 and developed mets July 2007. That's 21 months from diagnosis to mets.

[Lani]

her2neu breast cancer known to recur sooner and to have a shorter time from recurrence to death than her2- breast cancer --this latter information is included in numerous public lectures given by Dr Slamon

The time from recurrence to death figure he gives is 1 year vs 2 years for nonher2+ bc.

It is still unclear how herceptin changes all this in the long run particularly when given in the adjuvant setting to patients with early bc vs those with metastatic bc (there are many more years of data available in that setting)

I have never seen a graph of how her2+ER+ recurrence compares with
her2+ER- BC, ONLY HOW ER+ RECURS INCOMPARISON WITH ER-. Generally it is accepted that her2+ER+ tumors constitute <10% of ER+ tumors, so a graph of how all ER+ tumors behave may not be that influenced by the subset of those which are her2+ as well.

her2+ER- tumors constitute a larger % of all tumors that are ER-, so their contribution to the survival statistics will be greater and their behavior may more closely resemble those graphs (not entirely clear, but statistically more likely)

[jhandley]

Gina posted about this possibility along time ago..if you search for her post.

[KellyA]

I thought that the summer was one of the "good" months (something to do with the sun and vitamin D)? I don't know where I fall- probably in the spring- I found the lump in Feb or March, but it didn't get diagnosed until the first of May (however May here is like August somewhere else!!!!!)

Love, Kelly

[Lani]

I posted about these on several occasions myself, but only with respect to vitamin D. The melatonin literature has not been rigorous/definitive enough to allow too many conclusions to be drawn.

This was the first article I came across which studied both initial tumor presentation and recurrence by seasons--again, it is unfortunate that they could not subdivide the results by breast cancer subtype

[Lani]

if you use Becky's time of peak recurrence of 18-22 months, you would see why a tumor which was removed in the winter would recur in the spring.

As with most things, it is not so simple as JUST VITAMIN D, OTHERWISE THERE
woudn't be any tumors presenting in the summer.

As well as the biological reasons, there are societal reasons that many tumors maybe found in the summer as that is bathingsuit season when less clothes are worn and lumps are more likely to get detected as well as a period with more time-off when working women might be more likely to get their mammos.The clock starts ticking supposedly at the time of surgery, even if the lump was there longer.

These are just suppositions and I am sure there are gads of other reasonable ones...
.

[Gina]

and maybe even to primary tumor as well.

Hi, guys,

I know I have not been the posting maniac I used to be, but life, work, and a teenager with LEARNER's permit in Washington, DC, take over and keep one fairly busy...smile.

Yes, very early on, I noticed that my own liver mets were like on a clock. As I was already tracking tumor markers (ca 27/29 and CA 125 and CEA) back in 1998 and 1999 (not serum her-2 till early 2002, but since). Each year, the liver mets would recur at about the same time for 4 consecutive years making my tumor marker graph look more like a heartbeat EKG than some random graph. The numbers went up in about a 90 degree slope each time...then straight back down when I took herceptin.

I had never counted the months from my first DX (November 1997, primary 5cm tumor to right breast with 6 of 14 lymph nodes positive--stage 3b) till my first metastases (late spring, 1999) which would have been around 17 to 18 months, but what I did count was that after doing an entire year (1998) of aggressive traditional chemo CAF plus 100% strength taxotere(remember, back then, her-2 was not checked for and Herceptin was not approved until Nov. 1998) and radiation, all that only bought me 5 months supposedly "cancer free". I was so angry when the 12 tumor mets appeared in my liver the sizes of quarters, nickles, and dimes, after just literally having a completely clean CT 5 months prior... I swore, from that minute on that I would NEVER again do the traditional toxic "chemo" protocol--I was just fortunate to have had a really good oncologist back then, who somehow suspected the her-2 element to my disease, made me get both my original tumor block and my new liver tumor biopsy checked for her-2 and when we realized that I was ER- PR- but her-2 +++then he was willing to let me just try to take the herceptin by itself, without any chemo after I argued with him for days.

In only 5 weeks of standard Herceptin treatment which at that time was a loading dose of 4mg/kg the first week followed by 2mg/kg weekly doses, my tumor markers had returned to normal and the liver lesions, well, quite frankly, they just disappeared off the CT as though they had never been there. Later color photographs of my real liver (please don't even ask what I had to do to obtain those...LOL) did not even note scars where the tumors had been, even though the biopsy scar was still quite visible.

For me, the recurrence pattern was a worsening of the disease from late spring through summer and then sort of a cooling off period from fall and into the winter with the liver mets returning again the next spring and so forth.

One thing to think about though is WHERE the mets happen. For instance, in Chinese Medicine, the spring is a traditional time for the "liver" to show problems. Of course, when Chinese medicine mentions "LIVER" it does not exactly mean what we think of as the liver and tends to include the flow of the immune system up from the kidneys, into the spleen, and includes things like bile, liver, gallbladder and I am not sure what all as I really don't understand Chinese medicine as I am too analytical but it fascinates me nevertheless. My point being that there may be other things that Westerners may not think of that influence the timing of when mets hit certain organs but these factors could certainly include bio-rhythms or circadian rhythms of some sort that the Chinese, through centuries of practice may have picked up on...just a thought.

But I also have to agree with Lani about the bathing suit timeframe as I know A LOT of gals who get their primary dx in October, November, or December. This was true for me also. In Feb 1997, both my own self exams and my annual OB-GYN exam detected no lump. My boyfriend at that time said he felt something as early as April but as he was from Korea and the custom was not to discuss womanly things, he never told me until my DX was confirmed in November...sigh... Anyhow, over the summer, when I went to the beach, I sensed that my bathing suit was not fitting "quite right" and by the time my son had his tonsilectomy in October, there was no denying the very large and very hard lump on the inside upper quadrant of my right breast...when my sister saw it, she insisted that I get to my doctor IMMEDIATELY--I was a struggling single mom with a kid who was sick all the time with strep throat and the last thing I needed was another hospital surgery to pay, but nevertheless, the month after my son's surgery, I was on the operating table, and well, the rest is OLD OLD HISTORY...., but I am still here.

Although I KNOW you are all sick of hearing me say it..., I think the real reason that her-2 cancers at least often seem to display seasonal patterns is because at the very bottom of it all, lies a biological entity that is just as "alive" and just as tied into the seasons and magnetic earth field as we are. It is very common for many living things to show growing seasons through the spring and summer and become more latent or dormant throughout the fall and winter, but as many factors must be accounted for, it is almost impossible to do enough regression analysis to know for sure, but I think very soon, we will find out some real answers.

Thoughts???
Gina