Surgery As An Activator Of Dormant Distant Disease--food For Thought

ABSTRACT: Does surgery induce angiogenesis in breast cancer? Indirect evidence from relapse pattern and mammography paradox [International Journal of Surgery]
A significant bimodal relapse hazard pattern has been observed in two independent databases for patients untreated with adjuvant chemotherapy. This implies there is more than one mode of relapse. The earliest and most closely grouped relapses occur 8-10 months after surgery for young women with node-positive disease. Analysis of these data using computer simulation suggested that surgery probably instigated angiogenesis in dormant distant disease in approximately 20% of cases for premenopausal node-positive patients. We explore if this could explain the mammography paradox for women aged 40-49: an unexplained temporary excess in mortality for the screened population compared to controls. Calculations based on our data predict surgery-induced angiogenesis would accelerate disease by a median of two years and produce 0.11 early deaths per 1000 screened young women in the third year of screening. The predicted timing as well as the magnitude of excess mortality agree with trial data. Surgery-induced angiogenesis could account for the mammography paradox for women aged 40-49 and the bimodal relapse hazard pattern. According to the proposed biology, removing tumors could remove the source of inhibitors of angiogenesis or growth factors could appear in response to surgical wounding. While this needs confirmation, this could be considered when designing treatment protocols particularly for young women with positive nodes. It reinforces the need for close coordination between surgical resection and ensuing medical intervention. Women need to be advised of risk of accelerated tumor growth and early relapse before giving informed consent for mammography.

I have seen this argued before as a scenario.

Only an of the wall question but if some cancers are related to the omega six eicosanoid pathway / cox 2 / overstimulation of the emergency repair system, might surgery tip the level of stimulation of the emergency inflamatory repair system into cancer production in some circumstances.

So many questions.

It makes one wonder about options such as pre-excision chemo or RT

AND other potenial method of surgery / treatment if not already used such as tissue cryo ablation freezing, thermal, etc / direct injection of chemo into site etc things one has seen mentioned here and there.


RB

[al from Canada]

I've argued this pobably 5 or 6 times.....HER2 is a growth factor that can be stimulated by surgical assault, incorporating the P13K and COX2 pathways.

There was a very important trial taht used the continous infusion of 5FU during surgery and for days after, to knock-down surgical spread. There are 2 things at work here: the disloging of tumor cells and induction of mets and the upregulation of growth factors as a result of the body's response to healing. I think both these issues have to be addressed. I also think that is one of the reasons for the increase in neo-adjuvant therapy clinical trials.
Regards,
Al

Thanks Al,

You are a mine of information !

RB

[lu ann]

On September 26, 1991, I had a surgical biopsy, which confirmed malignancy. On October 7, 1991, I had a lumpectomy which resulted in mastectomy November 1, 1991, because I did not have clean margins free from cancer. I had adjuvant chemo consisting of cytoxin, 5-fu, and methotrexate. I did not have rad. tx. as tumor was less then 1 cm. and 22 lymph nodes were cancer free. I remained symptom free untill fall 2003 when I started to have severe backaches. I was dx. with mets Feb. 04. I have mets to mediastynym, spine, pelvis, and have pleural effusion. I believe had I of had rad.tx to the mastectomy site 15 years ago I would not of had a local reoccurance to my mediastynym, which spread throughout my body. Just My thoughts. Blessings, Lu Ann.

[Becky]

I agree that surgery can cause distant growth due to angiogenesis (the primary tumor does inhibit growth of distant small metastises) and growth factors. This is why I insisted on starting chemo 2 weeks after my lumpectomy and why I did not wait until Herceptin (my one year as an adjuvant) was over before I had my ovaries removed (never skipped a beat on treatments). I felt the overwhelming need to stay on the Herceptin/Arimidex combo for possible distant tumor control.


I plan on getting my first colonoscopy before the middle of June (when my year is up) for the same reason (as there could be a benign polp to remove - never know?)

Becky