В течение первых 4 нед гестации эмбрион не дифференцирован и воздействие химиопрепаратов происходит по принципу «все или ничего». Наиболее уязвимым для химиотерапии является период с 5 по 10-ю недели беременности, применение 1 цитостатика повышает риск развития пороков у плода до 10%, а нескольких – до 25%. Назначение терапии после 12 нед не ассоциировано с риском пороков развития, но приводит к задержке роста плода и панцитопении у новорожденных в 30%. Вероятность метастатического поражения плаценты и плода крайне низка и описана преимущественно для гематогенных опухолей. Курс лечения должен быть закончен за 3 нед до родов.
During the first 4 weeks of gestation, the embryo is not yet differentiated and exposure to chemotherapy occurs the all-or-nothing principle. Most vulnerable to chemotherapy is the period from 5 to 10 weeks of pregnancy, the use of 1 cytostatic increases the risk of malformations in the hearth up to 10%, and a few – up to 25%.
Prescription of therapy after 12 weeks is not associated with the risk of malformations. Development, but leads to delayed growth of the fetus and pancytopenia in newborns in 30%. Probability of a metostatic lesion the placenta and fetus is extremely low and is described primarily for hematogenous tumors. The course of treatment must be completed in 3 weeks. Before giving birth.
1. Hatem A, Azim Jr. Managing cancer during pregnancy. Springer, 2016; p. 191.
2. Ring AE, Smith IE, Ellis PA. Breast cancer and pregnancy. Ann Oncol 2005; 16 (12): 18555–60.
3. Beadle BM, Woodward WA, Middleton LP, Tereffe W. The impact of pregnancy on breast cancer outcomes in women before 35 years. Cancer 2009; 115 (6): 1174–84.
4. Amant F, Deckers S, Van Calsteren K, Loibl S. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer 2010; 46 (18): 3158–68.
5. Mir O, Berveiller P. Increased evidence for use of chemotherapy in pregnancy. Lancet Oncol 2012; 13 (9): 852–4.
6. Loibl S, Han SN, von Minckwitz G et al. Treatment of breast cancer during pregnancy: an observational study. Lancet Oncol 2012; 13 (9): 887–96.
7. Amant F, Halaska MJ, Fumagalli M, Dahl Steffensen K. Gynecologic cancers in pregnancy: guideline of a Second International Consensus Meeting. Int J Gynecol Cancer 2014; 24 (3): 394–03.
8. Mir O, Berveiller P, Pons G. Trastuzumsb – mechanism of action and use. N Engl J Med 2007: 357 (16): 1664–5.
9. Loibl S, Sdhmidt A, Gentilini O, Kaufman B. Breast cancer diagnosed during pregnancy: adapting recent advances in breast cancer care for pregnant patients. JAMA Oncol 2015; 1 (8): 1145–53.
10. Anderson GD. Pregnancy-indused changes in pharmacokinetics: a mechanistic-baced approach. Clin Pharmacokinet 2005; 44 (10): 989–1008.
11. Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol 2005; 6 (10): 780–9.
12. Krauer B, Dayer P, Anner R. Changes in serum albumin and alpha 1-acid glycoprotein concentrations during pregnancy: an analysis of fetal-maternal pairs. Br J Obstet Gynaecol 1984; 91 (9): 875–81.
13. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet 2004; 43 (8): 487–514.
14. Pacifici GM, Nottoli R. Placenta transferof drugs administered to the mother. Clin Pharmacokinet 1995; 28 (3): 235–69.
15. Nekhayeva IA, Nanovskaya TN, Hankins GD, Ahmed MS. Role of human placental efflux transporter P-glycoprotein in the transfer of buprenorphine, levo-alpha-acetylmethadol, and paclitaxel. Am J Perinatol 2006; 23 (7): 423–30.
16. D'Incalci M, Sessa C, Colombo N et al. Transplacental passage of cyclophosphamide. Cancer Treat Rep 1982; 66 (8): 1681–2.
17. Van Hasselt JG, van Calsteren K, Heyns L, Han S. Optimizing anticancer drug treatment in pregnancy cancer patients: pharmacokinetic analysis of gestation-indused changes for doxorubicin, epirubicin, docetaxel and paclitaxel. Ann Oncol 2014; 25 (10): 2059–65.
18. Eltorky M, Khare VK, Osborne P, Shanklin DR. Placental metastasis from maternal carcinoma. A report of three cases. J Reprod Med 1995; 40 (5): 399.
19. Baergen RN, Johnson D, Moore T, Benirschke K. Maternal melanoma metastatic to the placenta: a case report and review of the literature. Arch Pathol Lab Med 1997; 121 (5): 508.
20. Wang T, Hamann W, Hartge R. Structural aspects of a placenta from a case of maternal acute lymphatic leukaemia. Placenta 1983; 4 (2): 185.
21. Russell P, Laverty CR. Malignant melanoma metastases in the placenta: a case report. Pathology 1977; 9 (3): 251.
22. Sokol RJ, Hutchison P, Cowan D, Reed GB. Amelanotic melanoma metastatic to the placenta. Am J Obstet Gynecol 1976; 124 (4): 431.
23. Potter JF, Schoeneman M. Metastasis of maternal cancer to the placenta and fetus. Cancer 1970; 25 (2): 380.
24. Tsukamoto N, Kashimura Y, Sano M et al. Choriocarcinoma occurring within the normal placenta with breast metastasis. Gynecol Oncol 1981; 11 (3): 348.
25. Choriocarcinoma of the placenta. By the OSMA Committee on Maternal Health. Ohio State Med J 1975; 71 (3): 144.
26. Alexander A, Samlowski WE, Grossman D et al. Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant. J Clin Oncol 2003; 21 (11): 2179.
27. Altman JF, Lowe L, Redman B et al. Placental metastasis of maternal melanoma. J Am Acad Dermatol 2003; 49 (6): 1150.
28. Pavlidis N. Lung cancer during pregnancy: an emerging issue. Lung Cancer 2008; 59 (3): 279.
29. Sebire NJ, Jauniaux E. Fetal and placental malignancies: prenatal diagnosis and management. Ultrasound Obstet Gynecol 2009; 33 (2): 235.
30. Sotelo-Avila C, Graham M, Hanby DE, Rudolph AJ. Nevus cell aggregates in the placenta. A histochemical and electron microscopic study. Am J Clin Pathol 1988; 89 (3): 395.
________________________________________________
1. Hatem A, Azim Jr. Managing cancer during pregnancy. Springer, 2016; p. 191.
2. Ring AE, Smith IE, Ellis PA. Breast cancer and pregnancy. Ann Oncol 2005; 16 (12): 18555–60.
3. Beadle BM, Woodward WA, Middleton LP, Tereffe W. The impact of pregnancy on breast cancer outcomes in women before 35 years. Cancer 2009; 115 (6): 1174–84.
4. Amant F, Deckers S, Van Calsteren K, Loibl S. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer 2010; 46 (18): 3158–68.
5. Mir O, Berveiller P. Increased evidence for use of chemotherapy in pregnancy. Lancet Oncol 2012; 13 (9): 852–4.
6. Loibl S, Han SN, von Minckwitz G et al. Treatment of breast cancer during pregnancy: an observational study. Lancet Oncol 2012; 13 (9): 887–96.
7. Amant F, Halaska MJ, Fumagalli M, Dahl Steffensen K. Gynecologic cancers in pregnancy: guideline of a Second International Consensus Meeting. Int J Gynecol Cancer 2014; 24 (3): 394–03.
8. Mir O, Berveiller P, Pons G. Trastuzumsb – mechanism of action and use. N Engl J Med 2007: 357 (16): 1664–5.
9. Loibl S, Sdhmidt A, Gentilini O, Kaufman B. Breast cancer diagnosed during pregnancy: adapting recent advances in breast cancer care for pregnant patients. JAMA Oncol 2015; 1 (8): 1145–53.
10. Anderson GD. Pregnancy-indused changes in pharmacokinetics: a mechanistic-baced approach. Clin Pharmacokinet 2005; 44 (10): 989–1008.
11. Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol 2005; 6 (10): 780–9.
12. Krauer B, Dayer P, Anner R. Changes in serum albumin and alpha 1-acid glycoprotein concentrations during pregnancy: an analysis of fetal-maternal pairs. Br J Obstet Gynaecol 1984; 91 (9): 875–81.
13. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet 2004; 43 (8): 487–514.
14. Pacifici GM, Nottoli R. Placenta transferof drugs administered to the mother. Clin Pharmacokinet 1995; 28 (3): 235–69.
15. Nekhayeva IA, Nanovskaya TN, Hankins GD, Ahmed MS. Role of human placental efflux transporter P-glycoprotein in the transfer of buprenorphine, levo-alpha-acetylmethadol, and paclitaxel. Am J Perinatol 2006; 23 (7): 423–30.
16. D'Incalci M, Sessa C, Colombo N et al. Transplacental passage of cyclophosphamide. Cancer Treat Rep 1982; 66 (8): 1681–2.
17. Van Hasselt JG, van Calsteren K, Heyns L, Han S. Optimizing anticancer drug treatment in pregnancy cancer patients: pharmacokinetic analysis of gestation-indused changes for doxorubicin, epirubicin, docetaxel and paclitaxel. Ann Oncol 2014; 25 (10): 2059–65.
18. Eltorky M, Khare VK, Osborne P, Shanklin DR. Placental metastasis from maternal carcinoma. A report of three cases. J Reprod Med 1995; 40 (5): 399.
19. Baergen RN, Johnson D, Moore T, Benirschke K. Maternal melanoma metastatic to the placenta: a case report and review of the literature. Arch Pathol Lab Med 1997; 121 (5): 508.
20. Wang T, Hamann W, Hartge R. Structural aspects of a placenta from a case of maternal acute lymphatic leukaemia. Placenta 1983; 4 (2): 185.
21. Russell P, Laverty CR. Malignant melanoma metastases in the placenta: a case report. Pathology 1977; 9 (3): 251.
22. Sokol RJ, Hutchison P, Cowan D, Reed GB. Amelanotic melanoma metastatic to the placenta. Am J Obstet Gynecol 1976; 124 (4): 431.
23. Potter JF, Schoeneman M. Metastasis of maternal cancer to the placenta and fetus. Cancer 1970; 25 (2): 380.
24. Tsukamoto N, Kashimura Y, Sano M et al. Choriocarcinoma occurring within the normal placenta with breast metastasis. Gynecol Oncol 1981; 11 (3): 348.
25. Choriocarcinoma of the placenta. By the OSMA Committee on Maternal Health. Ohio State Med J 1975; 71 (3): 144.
26. Alexander A, Samlowski WE, Grossman D et al. Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant. J Clin Oncol 2003; 21 (11): 2179.
27. Altman JF, Lowe L, Redman B et al. Placental metastasis of maternal melanoma. J Am Acad Dermatol 2003; 49 (6): 1150.
28. Pavlidis N. Lung cancer during pregnancy: an emerging issue. Lung Cancer 2008; 59 (3): 279.
29. Sebire NJ, Jauniaux E. Fetal and placental malignancies: prenatal diagnosis and management. Ultrasound Obstet Gynecol 2009; 33 (2): 235.
30. Sotelo-Avila C, Graham M, Hanby DE, Rudolph AJ. Nevus cell aggregates in the placenta. A histochemical and electron microscopic study. Am J Clin Pathol 1988; 89 (3): 395.
Авторы
Ю.Э.Доброхотова, Е.И.Боровкова*
ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1
*katyanikitina@mail.ru
________________________________________________
Yu.E.Dobrokhotova, E.I.Borovkova*
N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1
*katyanikitina@mail.ru