- Email: [email protected]
Breast Cancer in Pregnancy: Report of 12 cases
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 146 (2009) 108–112
in the absence of other pathogens [1–5]. GBS vulvovaginitis presents with complaints of vulvar burning and clear or white vaginal discharge. The labia appear fiery-red, sometimes with fissures. It has been reported in both celibate and non-celibate women. Cultures contain GBS at a high multiplicity: >100,000,000 colony-forming units (CFU)/g of vaginal fluid or ++++ growth and decreased lactobacillus. GBS vaginitis is sometimes identified as aerobic vulvovaginitis. High colonization with GBS appears to provoke the release of cytokines causing inflammation and a severe decrease in lactobacillus. Current first-line treatment is oral penicillin or clindamycin. It was first noticed in 1976 in an original article in the American Journal of Obstetrics and Gynecology entitled ‘‘Antibiotic Treatment of Parturient Women Colonized With GBS’’ that oral antibiotics were ineffective at permanently decreasing asymptomatic GBS vaginal colonization. Women will culture negative for GBS immediately after 10–14-day regimens of antibiotics, but several days later the vagina is usually recolonized. An optimal treatment scheme for eliminating either asymptomatic or symptomatic vaginal GBS and simultaneously normalizing the vaginal ecosystem has not been established. Seven to 14-day regimens of oral antibiotics may or may not permanently eliminate the symptoms successfully. Adjunctive local therapies that have been used are estrogen cre`me, povidine gel, chlorhexidine gel and fresh garlic cloves cut in half. Fresh garlic releases allicin when cut. Allicin inhibits the growth of GBS in all GBS strains tested [6], most likely by interfering with the metabolism of cysteine and the function of the microtubules. Eight patients with confirmed symptomatic vaginal GBS of 6 months to 4 years duration, not resolved by course(s) of oral antibiotics, presented to our practice over a 4-year period. All presented with red labia, erythema and erosion of the vaginal walls. In addition, they all had one or more of the following: periodic burning sensation in the vagina, pain following intercourse, dyspareunia, periodic pain on urination, fissures, thick white odourless discharge, thick white putrid discharge, thick clear discharge, and nausea (Table 1). Ten to 14-day courses of clindamycin or penicillin had temporarily relieved but did not permanently resolve their symptoms. Several local antibiotics known to be effective against GBS were discussed with these clients: fresh garlic, chlorhexidine gel and/or povidine-iodine. The women all successfully resolved the symptoms by using half a freshly cut clove of garlic inserted vaginally at night and removed in the morning, for 3–6 weeks followed by maintenance doses of once every 2–4 days. The women were unable to obtain chlorhexidine gel at pharmacies and found povidine to be a nuisance as it stained their clothes. Table 1 Characteristics of symptomatic GBS vulvovaginitis cases. Age
Para
Sexually active
Symptoms in addition to erythema
Duration
Pen allergy
24 34 35
P0 G2P2 G2P2
Yes Yes Yes
6 months 8 months 1 year
Yes Yes No
36
P0
Yes
4 years
No
37 51
G2P2 P0
Yes Yes
8 months 4 years
No No
56
G1P1
Yes
11 months
No
65
P0
No
Burning, nausea Burning, nausea Burning, perianal fissures, thick white odourless disch Burning, thick white putrid disch Burning Burning, labial fissures, thick white putrid disch Burning during urination Clear putrid discharge
2 years
Yes
111
Until further research is done, it will not be known what the treatment(s) of choice for GBS vulvovaginitis is. References [1] Boyle D, Smith JR. Group B streptococcal vulvovaginitis. J R Soc Med 1997;90:298–9. [2] Gunter J, Ranallo L, Tawfik O. Inflammatory Streptococcal Vaginitis. Abstracts From the Third Annual Meeting of the International Infectious Disease Society for Obstetrics and Gynecology, New Orleans, LA. Infect Dis Obstet Gynecol 1998;6:14I–50I. [3] Monif GRG. Semiquantitative bacterial observations with group B streptococcal vulvovaginitis. Infect Dis Obstet Gynecol 1999;7:227–9. [4] Honig E, Mouton JW, van der Meijden WI. Can group B streptococci cause symptomatic vaginitis? Infect Dis Obstet Gynecol 1999;7(4):206–9. [5] Clark LR, Atendido M. Group B streptococcal vaginitis in postpubertal adolescent girls. J Adolesc Health 2005;36(5):437–40. [6] Cutler RR, Odent M, Hajj-Ahmad H, et al. In vitro activity of an aqueous allicin extract and a novel allicin topical gel formulation against Lancefield group B streptococci. J Antimicrob Chemother 2009;63(1):151–4.
Judy Slome Cohain* Alon Shvut 37, 90433, Israel *Tel.: +972 29931080 E-mail address: [email protected]
23 December 2008 doi:10.1016/j.ejogrb.2009.05.028
Breast Cancer in Pregnancy: Report of 12 cases
Dear Editor, The increasing incidence of Breast Cancer in Pregnancy (BCP) in the recent years has paralleled the raising age of childbearing in Western countries: in Italy the mean age at first delivery was 27.5 years in 1980 and 30.9 years in 2004 [1]. We report 12 cases of BCP and conducted a case–control, retrospective study to evaluate the overall survival of pregnant versus 24 non-pregnant women, matched for age and stage of breast cancer. Mean maternal age at diagnosis of BCP women was 33.5 2.1 years and gestational age averaged 28 9.4 weeks (means standard deviation). Eight patients underwent surgery during pregnancy (1 Patay Mastectomy and 7 quadrantectomy followed by lymph node dissection), plus chemotherapy with or without radiotherapy in the puerperium, The remaining 4 patients received neoadjuvant chemotherapy during pregnancy, due to a locally advanced T4 carcinoma and surgery after delivery (3 Madden and 1 Patay Mastectomy). The neoadjuvant chemotherapy consisted of epyrubicin alone (2 cycles) starting at 8 weeks in 1 patient and in 3 cycles of FEC (Fluorouracil, Epirubicin, Cyclophosphamide) in 3 women starting at gestational weeks 26, 27 and 28. Details on treatments are reported in Table 1. Six women had premature delivery, performed by cesarean section: in 3 women the earlier deliveries were requested by the patient willing to start or continue treatments including chemotherapy, without the possible harm for the fetus; in 2 patients labor was induced for preeclampsia at 35 and 33 weeks and in 1 patient for fetal distress at 28 weeks (Table 1). The time at delivery was 36.7 3.6 weeks. Newborn Apgar score were; min 1: 6.9 0.95; min 5: 8.3 0.75. Newborn weights were 2626.9 556.9 g. Four newborns were small for gestational age (cases 3, 5, 6, 11). Complications were observed in 2 premature newborns: 1 delivered at 33 weeks developed a respiratory distress syndrome successfully treated with oxygen and surfactant and 1 delivered at 28 weeks had a
112
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 146 (2009) 108–112
Table 1 Patient and newborn characteristics. Case pTNM
1 2 3 4 5 6 7 8 9 10 11 12
Time of Newborn’s delivery weight, g (weeks) (percentile)
Apgar score
T2N1M0 T1N1M0 T1N0M0
35 38 39
7/8 Patay Mastectomy No 8/9 Quadrantectomy + LN No 6/8–6/7 Quadrantectomy + LN No
T1N1M0 T4aN1M0 T4dN1M0 T1N0M0 T1N0M0 T4N2M1 T2N1M0 T4N1M0 T2N1M0
39 35 33 40 39 28 40 35 35
8/9 7/8 6/7 8/9 7/9 5/8 8/9 7/8 7/9
2400 (40th) 3000 (45th) 2800–2700 twins (10th) 3200 (50th) 2300 (25th) 1800 (25th) 3080 (40th) 3100 (40th) 1200 (90th) 3000 (40th) 2300 (25th) 2420 (40th)
Pre-delivery surgery
Quadrantectomy + LN No No No Quadrantectomy No Quadrantectomy No Quadrantectomy
Pre-delivery Post-delivery chemotherapy surgery
No FEC 3 cycles E 3 cycles No No E 3 cycles No E 3 cycles No
Post-delivery chemotherapy
Post-delivery Follow-up Current radiotherapy (months) status
No No No
FEC 6 cycles CMF 6 cycles FEC 6 cycles
No 50 + 10 Gy 50 + 10 Gy
24 84 31
Died Alive Alive
No Madden Mastectomy Patay Mastectomy Quadrantectomy No Madden Mastectomy No Madden Mastectomy No
FEC 6 cycles FEC 3 cycles FEC 6 cycles FEC 6 cycles FEC 6 cycles E + Taxol 6 cycles E + Taxol 6 cycles E + Taxol 6 cycles FEC 6 cycles
50 + 10 Gy No No 50 + 10 Gy 50 + 10 Gy No 50 + 10 Gy No 50 + 10 Gy
32 61 30 25 24 20 18 16 12
Alive Died Died Alive Alive Alive Alive Alive Alive
Abbreviations: FEC: Fluorouracil, Epirubicin, Cyclophosphamide; E: Epirubicin; CMF: Cyclophosphamide, Methotrexate, Fluorouracil; LN: lymphadenectomy
necrotizing enterocolitis, successfully treated with parenteral therapy. The follow-up of the newborns averaged 30 19.5 months and no malformations were observed in the newborns from 4 mothers who received chemotherapy during pregnancy, in agreement with previous reports [2]. In 3 patients exposed to antracyclines a low birth weight was observed, and in the patient who received epirubicin alone in the first trimester the delivery was premature (28 weeks), but the newborn’s weight was higher for gestational age. Previous studies reported spontaneous abortions in women exposed to chemotherapy in the first trimester [2,3], but our results are consistent with Berry et al. observing no such effect [4]. The major obstetrical problem associated with BCP in our series was premature delivery (50%), whose incidence was higher than observed in the general pregnant population, in fact in the year 2005 in Italy a 6.6% of preterm delivery has been registered [5]. Previous studies showed an incidence of preterm deliveries ranging from as low as 14.3% to more than 70% [2–4]. Our data are in between these 2 point estimates. Due to small series or single case reports, it is therefore difficult to reliably evaluate the real incidence of this phenomenon. Reasons for early labor induction in our patients were a request of starting as soon as possible adequate treatments and obstetrical complications of the mother (preeclampsia) or the fetus (intrauterine growth retardation), as previously reported [2–5]. Logrank test showed no significant differences between the overall survival curves (according to Kaplan–Meier) for pregnant and nonpregnant women (p = 0.88) with breast cancer. Due to the observed increase in early deliveries, patients with BCP should be closely monitored for fetal prematurity (including measurement of biophysical profile) and carefully evaluated to choose the right timing of delivery in order to avoid or prevent fetal early or late complications.
References [1] National Institute of Statistics (ISTAT). Health for All—Italy. Sistema informatico territoriale su sanita` e salute, updated dicembre 2007. Gruppo 1, Sez 4, cod 0210. Available at www.istat.it/sanita/Health. [2] Ring AE, Smith IE, Jones A, Shannon C, Galani E, Ellis PA. Chemotherapy for breast cancer during pregnancy. An 18-year experience from five London teaching hospitals. J Clin Oncol 2005;23:4192–7. [3] Giacalone PL, Laffargue F, Benos P. Chemotherapy for breast carcinoma during pregnancy: a French national survey. Cancer 1999;86:2266–72. [4] Berry DL, Theriault RL, Holmes FA, et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol 1999;17:855–61. [5] National Institute of Statistics (ISTAT). Condizioni di salute e ricorso ai servizi sanitari released 31-1-2008, tav 4.3.18, 7(3); 1999:855–61. www.istat.it/dati/ dataset/20080131_00/.
Marialuisa Framarino dei Malatestaa*, Mariagrazia Piccionia, Tiziana Gentilea, Paolo Sammartinoc, Bianca Roccab a Department of Gynecology, Perinatology and Health Care, University ‘‘Sapienza’’ School of Medicine, Via Bellini 14, 00198 Rome, Italy b Department of Pharmacology, Catholic University School of Medicine, Rome, Italy c Department of Surgery ‘Pietro Valdoni’, University ‘‘Sapienza’’ School of Medicine, Rome, Italy *Corresponding
author. Tel.: +39 068848883; fax: +39 0685301544 E-mail address: [email protected] (ML. Framarino dei Malatesta) 14 October 2008 doi:10.1016/j.ejogrb.2009.05.029
in the absence of other pathogens [1–5]. GBS vulvovaginitis presents with complaints of vulvar burning and clear or white vaginal discharge. The labia appear fiery-red, sometimes with fissures. It has been reported in both celibate and non-celibate women. Cultures contain GBS at a high multiplicity: >100,000,000 colony-forming units (CFU)/g of vaginal fluid or ++++ growth and decreased lactobacillus. GBS vaginitis is sometimes identified as aerobic vulvovaginitis. High colonization with GBS appears to provoke the release of cytokines causing inflammation and a severe decrease in lactobacillus. Current first-line treatment is oral penicillin or clindamycin. It was first noticed in 1976 in an original article in the American Journal of Obstetrics and Gynecology entitled ‘‘Antibiotic Treatment of Parturient Women Colonized With GBS’’ that oral antibiotics were ineffective at permanently decreasing asymptomatic GBS vaginal colonization. Women will culture negative for GBS immediately after 10–14-day regimens of antibiotics, but several days later the vagina is usually recolonized. An optimal treatment scheme for eliminating either asymptomatic or symptomatic vaginal GBS and simultaneously normalizing the vaginal ecosystem has not been established. Seven to 14-day regimens of oral antibiotics may or may not permanently eliminate the symptoms successfully. Adjunctive local therapies that have been used are estrogen cre`me, povidine gel, chlorhexidine gel and fresh garlic cloves cut in half. Fresh garlic releases allicin when cut. Allicin inhibits the growth of GBS in all GBS strains tested [6], most likely by interfering with the metabolism of cysteine and the function of the microtubules. Eight patients with confirmed symptomatic vaginal GBS of 6 months to 4 years duration, not resolved by course(s) of oral antibiotics, presented to our practice over a 4-year period. All presented with red labia, erythema and erosion of the vaginal walls. In addition, they all had one or more of the following: periodic burning sensation in the vagina, pain following intercourse, dyspareunia, periodic pain on urination, fissures, thick white odourless discharge, thick white putrid discharge, thick clear discharge, and nausea (Table 1). Ten to 14-day courses of clindamycin or penicillin had temporarily relieved but did not permanently resolve their symptoms. Several local antibiotics known to be effective against GBS were discussed with these clients: fresh garlic, chlorhexidine gel and/or povidine-iodine. The women all successfully resolved the symptoms by using half a freshly cut clove of garlic inserted vaginally at night and removed in the morning, for 3–6 weeks followed by maintenance doses of once every 2–4 days. The women were unable to obtain chlorhexidine gel at pharmacies and found povidine to be a nuisance as it stained their clothes. Table 1 Characteristics of symptomatic GBS vulvovaginitis cases. Age
Para
Sexually active
Symptoms in addition to erythema
Duration
Pen allergy
24 34 35
P0 G2P2 G2P2
Yes Yes Yes
6 months 8 months 1 year
Yes Yes No
36
P0
Yes
4 years
No
37 51
G2P2 P0
Yes Yes
8 months 4 years
No No
56
G1P1
Yes
11 months
No
65
P0
No
Burning, nausea Burning, nausea Burning, perianal fissures, thick white odourless disch Burning, thick white putrid disch Burning Burning, labial fissures, thick white putrid disch Burning during urination Clear putrid discharge
2 years
Yes
111
Until further research is done, it will not be known what the treatment(s) of choice for GBS vulvovaginitis is. References [1] Boyle D, Smith JR. Group B streptococcal vulvovaginitis. J R Soc Med 1997;90:298–9. [2] Gunter J, Ranallo L, Tawfik O. Inflammatory Streptococcal Vaginitis. Abstracts From the Third Annual Meeting of the International Infectious Disease Society for Obstetrics and Gynecology, New Orleans, LA. Infect Dis Obstet Gynecol 1998;6:14I–50I. [3] Monif GRG. Semiquantitative bacterial observations with group B streptococcal vulvovaginitis. Infect Dis Obstet Gynecol 1999;7:227–9. [4] Honig E, Mouton JW, van der Meijden WI. Can group B streptococci cause symptomatic vaginitis? Infect Dis Obstet Gynecol 1999;7(4):206–9. [5] Clark LR, Atendido M. Group B streptococcal vaginitis in postpubertal adolescent girls. J Adolesc Health 2005;36(5):437–40. [6] Cutler RR, Odent M, Hajj-Ahmad H, et al. In vitro activity of an aqueous allicin extract and a novel allicin topical gel formulation against Lancefield group B streptococci. J Antimicrob Chemother 2009;63(1):151–4.
Judy Slome Cohain* Alon Shvut 37, 90433, Israel *Tel.: +972 29931080 E-mail address: [email protected]
23 December 2008 doi:10.1016/j.ejogrb.2009.05.028
Breast Cancer in Pregnancy: Report of 12 cases
Dear Editor, The increasing incidence of Breast Cancer in Pregnancy (BCP) in the recent years has paralleled the raising age of childbearing in Western countries: in Italy the mean age at first delivery was 27.5 years in 1980 and 30.9 years in 2004 [1]. We report 12 cases of BCP and conducted a case–control, retrospective study to evaluate the overall survival of pregnant versus 24 non-pregnant women, matched for age and stage of breast cancer. Mean maternal age at diagnosis of BCP women was 33.5 2.1 years and gestational age averaged 28 9.4 weeks (means standard deviation). Eight patients underwent surgery during pregnancy (1 Patay Mastectomy and 7 quadrantectomy followed by lymph node dissection), plus chemotherapy with or without radiotherapy in the puerperium, The remaining 4 patients received neoadjuvant chemotherapy during pregnancy, due to a locally advanced T4 carcinoma and surgery after delivery (3 Madden and 1 Patay Mastectomy). The neoadjuvant chemotherapy consisted of epyrubicin alone (2 cycles) starting at 8 weeks in 1 patient and in 3 cycles of FEC (Fluorouracil, Epirubicin, Cyclophosphamide) in 3 women starting at gestational weeks 26, 27 and 28. Details on treatments are reported in Table 1. Six women had premature delivery, performed by cesarean section: in 3 women the earlier deliveries were requested by the patient willing to start or continue treatments including chemotherapy, without the possible harm for the fetus; in 2 patients labor was induced for preeclampsia at 35 and 33 weeks and in 1 patient for fetal distress at 28 weeks (Table 1). The time at delivery was 36.7 3.6 weeks. Newborn Apgar score were; min 1: 6.9 0.95; min 5: 8.3 0.75. Newborn weights were 2626.9 556.9 g. Four newborns were small for gestational age (cases 3, 5, 6, 11). Complications were observed in 2 premature newborns: 1 delivered at 33 weeks developed a respiratory distress syndrome successfully treated with oxygen and surfactant and 1 delivered at 28 weeks had a
112
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 146 (2009) 108–112
Table 1 Patient and newborn characteristics. Case pTNM
1 2 3 4 5 6 7 8 9 10 11 12
Time of Newborn’s delivery weight, g (weeks) (percentile)
Apgar score
T2N1M0 T1N1M0 T1N0M0
35 38 39
7/8 Patay Mastectomy No 8/9 Quadrantectomy + LN No 6/8–6/7 Quadrantectomy + LN No
T1N1M0 T4aN1M0 T4dN1M0 T1N0M0 T1N0M0 T4N2M1 T2N1M0 T4N1M0 T2N1M0
39 35 33 40 39 28 40 35 35
8/9 7/8 6/7 8/9 7/9 5/8 8/9 7/8 7/9
2400 (40th) 3000 (45th) 2800–2700 twins (10th) 3200 (50th) 2300 (25th) 1800 (25th) 3080 (40th) 3100 (40th) 1200 (90th) 3000 (40th) 2300 (25th) 2420 (40th)
Pre-delivery surgery
Quadrantectomy + LN No No No Quadrantectomy No Quadrantectomy No Quadrantectomy
Pre-delivery Post-delivery chemotherapy surgery
No FEC 3 cycles E 3 cycles No No E 3 cycles No E 3 cycles No
Post-delivery chemotherapy
Post-delivery Follow-up Current radiotherapy (months) status
No No No
FEC 6 cycles CMF 6 cycles FEC 6 cycles
No 50 + 10 Gy 50 + 10 Gy
24 84 31
Died Alive Alive
No Madden Mastectomy Patay Mastectomy Quadrantectomy No Madden Mastectomy No Madden Mastectomy No
FEC 6 cycles FEC 3 cycles FEC 6 cycles FEC 6 cycles FEC 6 cycles E + Taxol 6 cycles E + Taxol 6 cycles E + Taxol 6 cycles FEC 6 cycles
50 + 10 Gy No No 50 + 10 Gy 50 + 10 Gy No 50 + 10 Gy No 50 + 10 Gy
32 61 30 25 24 20 18 16 12
Alive Died Died Alive Alive Alive Alive Alive Alive
Abbreviations: FEC: Fluorouracil, Epirubicin, Cyclophosphamide; E: Epirubicin; CMF: Cyclophosphamide, Methotrexate, Fluorouracil; LN: lymphadenectomy
necrotizing enterocolitis, successfully treated with parenteral therapy. The follow-up of the newborns averaged 30 19.5 months and no malformations were observed in the newborns from 4 mothers who received chemotherapy during pregnancy, in agreement with previous reports [2]. In 3 patients exposed to antracyclines a low birth weight was observed, and in the patient who received epirubicin alone in the first trimester the delivery was premature (28 weeks), but the newborn’s weight was higher for gestational age. Previous studies reported spontaneous abortions in women exposed to chemotherapy in the first trimester [2,3], but our results are consistent with Berry et al. observing no such effect [4]. The major obstetrical problem associated with BCP in our series was premature delivery (50%), whose incidence was higher than observed in the general pregnant population, in fact in the year 2005 in Italy a 6.6% of preterm delivery has been registered [5]. Previous studies showed an incidence of preterm deliveries ranging from as low as 14.3% to more than 70% [2–4]. Our data are in between these 2 point estimates. Due to small series or single case reports, it is therefore difficult to reliably evaluate the real incidence of this phenomenon. Reasons for early labor induction in our patients were a request of starting as soon as possible adequate treatments and obstetrical complications of the mother (preeclampsia) or the fetus (intrauterine growth retardation), as previously reported [2–5]. Logrank test showed no significant differences between the overall survival curves (according to Kaplan–Meier) for pregnant and nonpregnant women (p = 0.88) with breast cancer. Due to the observed increase in early deliveries, patients with BCP should be closely monitored for fetal prematurity (including measurement of biophysical profile) and carefully evaluated to choose the right timing of delivery in order to avoid or prevent fetal early or late complications.
References [1] National Institute of Statistics (ISTAT). Health for All—Italy. Sistema informatico territoriale su sanita` e salute, updated dicembre 2007. Gruppo 1, Sez 4, cod 0210. Available at www.istat.it/sanita/Health. [2] Ring AE, Smith IE, Jones A, Shannon C, Galani E, Ellis PA. Chemotherapy for breast cancer during pregnancy. An 18-year experience from five London teaching hospitals. J Clin Oncol 2005;23:4192–7. [3] Giacalone PL, Laffargue F, Benos P. Chemotherapy for breast carcinoma during pregnancy: a French national survey. Cancer 1999;86:2266–72. [4] Berry DL, Theriault RL, Holmes FA, et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol 1999;17:855–61. [5] National Institute of Statistics (ISTAT). Condizioni di salute e ricorso ai servizi sanitari released 31-1-2008, tav 4.3.18, 7(3); 1999:855–61. www.istat.it/dati/ dataset/20080131_00/.
Marialuisa Framarino dei Malatestaa*, Mariagrazia Piccionia, Tiziana Gentilea, Paolo Sammartinoc, Bianca Roccab a Department of Gynecology, Perinatology and Health Care, University ‘‘Sapienza’’ School of Medicine, Via Bellini 14, 00198 Rome, Italy b Department of Pharmacology, Catholic University School of Medicine, Rome, Italy c Department of Surgery ‘Pietro Valdoni’, University ‘‘Sapienza’’ School of Medicine, Rome, Italy *Corresponding
author. Tel.: +39 068848883; fax: +39 0685301544 E-mail address: [email protected] (ML. Framarino dei Malatesta) 14 October 2008 doi:10.1016/j.ejogrb.2009.05.029