15 september 2003: Bron: Nature en Journal of Cancer.

Dat het moment van opereren in de eerste helft of tweede helft van de menstruatie bepalend kan zijn, zoals de studie met muizen hieronder beschreven , lijkt te bewijzen, voor de kansen op een recidief en/of uitzaaiingen is al een studieresultaat - gedaan bij 565 vrouwen - gepubliceerd op 1 mei 2002 in the Journal of Cancer van het NCI. Vrouwen die in de tweede helft van hun menstruatiecyclus werden geopereerd hadden 10% minder kans op een recidief en/of uitzaaiingen dan vrouwen die in de eerste helft van hun menstruatiecyclus werden geopereerd. Je kunt je afvragen waarom chirurgen en oncologen daar dan niet verder rekening mee houden lijkt mij.

Bron: Journal of Cancer

Mastectomy and Oophorectomy by Menstrual Cycle Phase in Women With Operable Breast Cancer
Richard R. Love, Nguyen Ba Duc, Nguyen Van Dinh, Tian-Zhen Shen, Thomas C. Havighurst, D. Craig Allred, David L. DeMets

Affiliations of authors: R. R. Love, Department of Medicine, Section of Medical Oncology, University of Wisconsin School of Medicine, Madison; N. B. Duc, N. V. Dinh, Hospital K, National Cancer Institute, Hanoi, Vietnam; T.-Z. Shen, People's Hospital of Haimen City, Haimen, Jiangsu, China; T. C. Havighurst, Department of Biostatistics and Medical Informatics, University of Wisconsin; D. C. Allred, Department of Pathology, Baylor College of Medicine, Houston, TX; D. L. DeMets, Department of Biostatistics and Medical Informatics, University of Wisconsin.

Correspondence to: Richard R. Love, M.D., M.S., 610 Walnut St., 256 WARF, Madison, WI 53705 (email: rrlove@facstaff.wisc.edu).

Background: It is unclear whether the phase of the menstrual cycle in which primary surgical treatment occurs influences disease-free survival (DFS) and overall survival (OS) in premenopausal women with breast cancer. We investigated this question in the context of a clinical trial comparing mastectomy alone with mastectomy plus adjuvant oophorectomy and tamoxifen in premenopausal women with operable breast cancer.

Methods: The date of the first day of the last menstrual period (LMP) was used to estimate the phase of the menstrual cycle when the surgeries were done. Follicular phase was defined as day 1–14 from LMP. Luteal phase was defined as day 15–42 from LMP. DFS and OS statistics were determined and analyzed by Cox proportional hazards ratios and Kaplan–Meier methods. All statistical tests were two-sided.

Results: We analyzed results for 565 women who reported an LMP within 42 days before surgery. For women in the mastectomy only arm (n = 289), there were no differences in DFS or OS by menstrual cycle phase. For women in the adjuvant treatment arm (n = 276), those whose surgery occurred during the luteal phase (n = 158) had better DFS (relative risk = 0.54; 95% confidence interval = 0.32 to 0.96; P = .02) and OS (RR = 0.53; 95% CI = 0.30 to 0.95; P = .03) than those whose surgery occurred during the follicular phase (n = 118). Moreover, women whose surgery occurred during the luteal phase and who received adjuvant therapy had better 5-year DFS than did women whose surgery occurred during the follicular phase (84%; 95% CI = 78% to 90% versus 67%; 95% CI = 58% to 78%; P = .02); they also had better OS (85%; 95% CI = 78% to 92% versus 75%; 95% CI = 66% to 84%; P = .03).

Conclusions: The phase of the menstrual cycle at which surgery was done had no impact on survival for women who received mastectomy only. However, women who received a mastectomy and surgical oophorectomy and tamoxifen during the luteal phase had better outcomes than women who received surgery during the follicular phase.

Bron: Nature d.d. 15 september 2003

Operatie bij kankerpatiënten in bepaalde tijd van menstruatiecyclus kan van grote invloed zijn op recidiefkansen en uitzaaiingen.

Hoewel verschillende studies eerder nooit het echte bewijs hebben kunnen leveren, hoewel de studie in Winconsin - zie hierboven - dit bewijs wel leverde, heeft nu een studie met muizen aangetoond dat een operatie bij kankerpatiënten in een bepaalde tijd van de menstruatiecyclus wel degelijk van invloed kan zijn op het later ontstaan van uitzaaiingen en dus van een recidief. Dit meldt Nature in hun editie van afgelopen week d.d. 9 september 2003. Bijna een derde van de muizen die van tevoren waren ingespoten met melanoomcellen en progesteron en daaraan dan werden geopereerd ontwikkelden darna eierstokkanker. de muizen die met oestrogeen werden ingespoten naast alle andere vertoonden geen enkele kankercellen. Deze conclusie geldt als hoogsignificant en de onderzoeksleidster Ann Chambers van het London Regional Cancer Centre in London meldt dan ook dat meer onderzoek dringend nodig is. Retrospectieve studies hebben al eerder geprobeerd hier uitsluitsel over te geven, maar omdat deelneemsters pas achteraf werd gevraagd naar hun menstruatiecyclus enz. waren deze studies moeilijk echt goed te analyseren. Nu lopen er verschillende grote studies waarbij de vrouwen heel nauwkeurig hun menstruatiecyclus vastleggen en bijhouden. Hopelijk komt dan ook snel duidelijkheid over dit opzienbarende resultaat.

Bron: Nature

Menstrual phase influences cancer spread in mice Study feeds controversy over timing of tumour surgery. 9 September 2003

Hormone levels may affect tumor spread.
© Corbis

The phase of a mouse's menstrual cycle can dramatically alter the risk of cancer spreading, say researchers in Canada. The finding fuels the debate over whether women's cancer surgery should be timed to specific menstrual stages.

Some studies on breast-cancer patients have found that women whose tumours are removed in a particular phase of their menstrual cycle are more likely to get secondary tumours - called metastases - and die earlier. But other studies have found no such link.

Nearly a third of mice injected with skin-cancer cells when their levels of the hormone progesterone was high developed ovarian tumours, reports a team led by Ann Chambers of the London Regional Cancer Centre in London, Canada1. Those injected when oestrogen was high showed no such cancer. "We were so startled," Chambers says.

The study implies that other tumours besides breast cancer might be more likely to spread if they are operated on at particular times. This might be particularly crucial for surgery on young tumours which might slough off potentially migrating cancer cells before they would naturally spread, Chambers suggests.

The study is important, says Richard Love, who studies breast cancer at the University of Wisconsin in Madison, because it shows that hormones might promote metastasis by working on the tissues in which a drifting cancer cell implants. Until now, most research has focused on how hormones change the tumour itself.

But it is too early to consider rescheduling operations, warns breast-cancer researcher Gabriel Hortobagyi of the University of Texas in Houston. The picture may be very different in women from that in mice. "It adds another reason to do a proper clinical trial," he says.

Clinical clash

The results of clinical studies about menstrual phase and metastasis are conflicting, mainly because data are often gathered retrospectively, and menstrual phase was not precisely recorded. What's more, the rolling menstrual cycle, with its subtly shifting hormone patterns, is difficult to divide into neat stages.

Large-scale prospective studies are now under way in the United States in which women's blood hormone levels are measured accurately before breast-cancer surgery. "Everything else is just background noise," says Hortobagyi.

It's a stretch to say it directly applies to patients
Ann Chambers
London Regional Cancer

Researchers are not sure how shifting levels of oestrogen and progesterone might trigger metastasis. Chambers speculates that the hormones alter the structure of the ovary or stimulate the growth of blood vessels, making them more receptive to implantation or development of cancer cells.

If the protective hormones - or other molecules - can be identified, they might even be administered before surgery, Chambers suggests, an idea that might be tested using her mouse model.

Vantyghem, S.A., Postenka, C.O. & Chambers, A.F. Estrous cycle influences organ-specific metastasis of B16F10 cells. Cancer Research, 63, 4763 - 4765, (2003).

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