The diagnosis and management of breast problems during pregnancy and lactation

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The Diagnosis and Management of Breast Problems During Pregnancy and Lactation Carol E.H. Scott-Conner,

MD, PhD, Stephen J. Schorr, MD, Jxkson,

BACKGROUND: In addition to mastitis, lactational breast abscesses, and several other benign conditions unique to the puerperium, pregnant women may develop any of the other breast problems seen in the nonpregnant female population. This review deals with the diagnosis and management of breast problems during pregnancy and lactation. DATA SOURCES: A literature review of the evaluation, technique of biopsy, and treatment of cancer in pregnant women was conducted. CONCLUSIONS: The most common problems fall into a spectrum of infectious complications from milk stasis or mastitis to frank abscess formation. Galactoceles, noninfected milk-filled cysts, present as tender masses; aspiration is both diagnostic and curative. Benign fibroadenomas occasionally enlarge significantly or infarct during pregnancy. A physiologic nipple discharge is common during pregnancy, and may be bloody. Rare cases of massive breast hypertrophy during pregnancy have been reported. The mortality of breast cancer during pregnancy is related to delay: compared stage-for-stage with nonpregnant controls, the prognosis is similar. As a general rule, the cancer should be treated surgically and the pregnancy may be allowed to progress. Am J Surg. 1995;170:401-405.

rrgnancy is associated with profound changes of the maternal breast. A sequence of physiologic events occurs during pregnancy to prepare the breast as the priP mary organ for infant nurturing. This is most evident by a substantial mcrease m breast size and weight, beginning in the first trimester. The hormonal milieu of pregnancy in~luces prolitrrative changes consisting primarily of lobular

From the Department of Surgery (CEHS-C), and the Department of Obstetrics and Gynecology (SJS), University of Mississippi Medical Center, Jackson, Mississippi. Dr. Scott-Conner is currently affiliated with the Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa. This work was supported in part by the Vicksburg Hospital Medical Foundation, Vicksburg, Mississippi. Requests for reprints should be addressed to Carol E.H. ScottConner, MD, PhD, Department of Surgery, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, #1516JCP, Iowa City, Iowa 52242-1086. Manuscript submitted August 22, 1994 and accepted in revised form December 23, 1994.

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and alveolar growth. By the end of gestation, breast weight of approximately 200 g normal resting breast weight will have doubled to 400 g. Mammary blood flow increases hy almost 200% with new capillary formation and accumulation of fat within the alveolar cells.’ Histologic changes reflect increased secretory activity within the lactating breast. Dilated acini are lined by low cuboidal epithelium. In stark contrast to nonpregnant, reproductive-age breast tissue that is predominately stroma, most of the puerperal breast is glandular epithelium with little intervening strotn;]. C&strum is produced before delivery in small amounts; significant milk production begins 2 to i days after delivery as high prolactin levels remain, while ovarian and placental hormonal levels are falling rapidly. Ovarian and placental hormones inhibit the lactogenic effect of prolactin prior to delivery. Stimulated by sucking, prolactin-lndllced lactation continues virtually indefinitely until milk IS no longer regularly removed from the breast.‘,’ During lactatron, apocrine and merocrine secretion of alveolar cells occurs. The protein and lactose components of mrlk are produc,ed by different mechanisms. Two days after nursing and meclranical removal of milk are stopped, milk production fddlls rapidly. Involution of the breast follows rapidly after lactation ceases. Pregnant and lactating women may develop any of the breast lesions seen in nonpregnant women, and, in addition, are prone to certain problems unique to pregnancy. Although most lesions are benign, a small but srgnificant number of breast cancers occur in pregnant women.’ The physiologic changes associated with pregnancy make it difficult to detect or evaluate masses. Thus review twill describe the diagnosis and management of breast prohlcms encountered during pregnancy and lactation.

BENIGN BREAST PROBLEMS Milk Stasis, Mastitis, and Breast Abscesses The most common benign breast problems in pregnancy and puerperium form a continuum of infectious complications.“~’ Milk stasis (breast engorgement) provides a lactoserich culture medmm for bacteria entering via the terminal ducts of the nipple. This may result in pucrperal mastitis, which in turn can progress into a breast ahsccss. All cause fever, pain, and swelling of the breast. Treatment is based upon accurate differentiation of the three entities, which is usually established by physical examination. Milk leukocyte counts and quantitative bacterial cuhurcs may he helpful (Table). Puerperal mastitis affects 2% of lactatmg women. There are two principal forms of mastitis, epidemic and nonepidemic.’ Nonepidemic (sporadic) mastitis usually occurs 2 or more weeks after delivery and rarely progresses to breast abscess. Epidemrc mastitis occurs within 4 days
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TABLE Milk Leukocyte Counts and Quantitative Bacterial Cultures in Infectious Breast Conditions

Milk stasis Noninfectious inflammation Infectious mastitis Data adapted

Leukocytes

Bacteria

c106/mL >106/mL 2106/mUmL

403 403 >103

from Thornsen et al, 19M5

within a nursery and hence to the nursing mother. The portal of entry is the nipple; cracked skin, poor hygiene, and breast engorgement all contribute. Staphylococcus aureus is the most common causative organism.7 Therapy consists of a 7- to lo-day course of an antistaphylococcal oral antibiotic, such as penicillin G or dicloxacillin. In cases of sporadic mastitis, breast feeding may continue during treatment and probably aids in recovery. 7,8Breast abscess should be suspected if the symptoms of mastitis do not resolve after several days of antibiotic treatment. Most breast abscesses occur within the first month of breast feeding and are more likely to afflict young, inexperienced mothers not practicing proper hygiene. A second peak of incidence occurs at the time of weaning, when the breasts become engorged and milk is allowed to stagnate within the ducts. In contrast to mastitis, which responds rapidly to antibiotics, an abscess generally requires both antibiotics and drainage for complete resolution.5 Drainage may be accomplished by aspiration, which may need to be repeated several times.’ The breast must be kept empty of milk, which is an excellent culture medium. In some patients, it is difficult to determine whether the process is purely cellulitic or if an abscess has formed. Treatment with antibiotics and observation usually clarifies this situation. Breast feeding may continue using the contralateral side. If necessary, lactation may be suppressed. The infant should not be allowed to nurse from the breast with the abscess, particularly when the abscess is staphylococcal, because pneumonia, lung abscesses, and death of the infant can result.‘O If incisional drainage is required, biopsy should be performed to rule out inflammatory carcinoma. This procedure is discussed in the Diagnosis section. Galactoceles Galactoceles are simple, milk-filled cysts that probably form as a consequence of ductal obstruction.“J2 They present as tender masses, usually in the periphery of the breast. Diagnostic aspiration is usually curative.13 Mammography is rarely needed; however, the mammographic appearance of a galactocele is characteristic, owing to the partially fatty density of the contained milk.14 Ice packs and breast support may be helpful. Repeat aspiration may be needed. Surgery is rarely indicated. There is no clear association between galactoceles and the tendency to form breast cysts associated with fibrocystic disease. Benign Tumors Fibroadenomas are benign tumors that are easy to recog nize clinically because they are well-demarcated, smooth, and mobile. As with any solitary breast mass, excision is advised. During pregnancy, fibroadenomas often increase in size 402

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and may show lactational histologic changes.‘J2J3 This is one reason why removal is advised prior to pregnancy, even in teenagers (where the risk of cancer is small and the clinical diagnosis of fibroadenoma virtually 100% accurate). Infarction can occur during pregnancy and lactation, and is generally asymptomatic.’ Occasionally a fibroadenoma will grow in response to the hormonal stimulus of pregnancy, and then infarct, causing a significant increase in size and pain. It may then be confused with cancer.’ Excision is required to confirm the diagnosis. Mammograms of older women often show calcified fibroadenomas, which may be the footprints of old infarcts.’ Nodular lactational hyperplasia or lactating adenomas may be true adenomas or simply represent focal hyperplasia.12 They are palpable as single or multiple freely mobile masses and appear during pregnancy, or early post partum.15 Normal breast tissue occasionally infarcts during pregnancy or lactation.16 The result is a palpable, often tender, mass. This mass must be differentiated from breast cancer.17 Often biopsy is necessary. Mammary hamartomas are benign tumors very similar to fibroadenomasL8 Often they are diagnosed for the first time after pregnancy, when postlactational involution makes the breasts shrink dramatically. The tumor then becomes apparent. These tumors are characteristically smooth and well encapsulated. The term “breast within breast” originated from the old German references and aptly describes the histologic and gross characteristics. Histologically, elements of fatty, stromal, and ductal tissue are all present. It is very likely that, like fibroadenomas, previously inapparent hamartomas enlarge during pregnancy. Excision is the treatment of choice, and enucleation of even large lesions leaves no residual cosmetic deformity because the amount of remaining breast tissue is comparable to the contralateral side. Breast Hypertrophy With Pregnancy Rarely, the physiologic breast enlargement that normally occurs during pregnancy is exaggerated to the point that gigantomastia results.19-21This is an extremely rare condition that may progress to the extent of skin necrosis, ulceration, or hemorrhage.22 Pseudohyperparathyroidism has been associated with this condition.23 In most cases, breasts will regress post partum, but the condition may recur with subsequent preg nancies.21F22Reduction mammoplasty should be considered.” Nipple Discharge The epithelial proliferation that normally occurs during pregnancy occasionally causes bloody nipple discharge during the second or third trimester.24 Cytology may be misleading; normal proliferative changes appear ominous. The treatment is observation and reassurance, as the condition is normally self-limited.24 If the discharge persists more than 2 months after delivery, further investigation should be undertaken. Special Considerations: Nursing After Ductal Excision Partial or complete ductal excision is occasionally required for nipple discharge, intraductal papilloma, or subareolar masses. Subsequent pregnancy may raise the question of whether or not nursing may be allowed. Generally, lactation should be deferred for 1 year after this procedure. Breast feedOCTOBER

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ing ih usually not possible from the operated side: feeding from the conCr&teral breast can progress normall~-.“5 BREAST CANCER Approximately 1% to 2% of breast cancers in women are diagnosed during pregnancy; this correlates with a rate of 10 tc> 39 cases per 100,000 deliveries.” In one series, 10% of breast cimcrrs diagnosed in women less than 40 years of age were diagnosed during pregnancy.’ Recent tendencies to defer childbearing until later in life may increase the incidence, a\ more gravid women are of an age to develop breast cancer.?’ Recognizing that breast cancer is probably present for 8 to IO yeara before it becomes clinically detectahle, many women have pn,bably been pregnant durIng the development of their cancers without recognizing the f;lct. Diagnosis Careful serial examination is still the cornerstone of derection, and is even more important during pregnancy when the physiologic alterations in breast tissue make evaluation difficult. A baseline breast examination at the time of the first c>hstetrical visit is critical. As pregnancy progresses, the significant Increase in breast mass, density, and vascularity will make evaluation of mass lesions difficult and may create the illusion that a small l&ion has resoIved.!H,!‘) Mammography may be of benefit; however, the increased density, vascularity, and water content of the hrca>ts make it difficult to detect small lesions. Ultrasound is useful in differentiating cystic from solid lesions. A high index of suspicicm and the willingness to aspirate and/or excise suspicious masses remain the best apprc,ach. Tht most comm<>n mass lesions during pregnancy (as in the nonpregnmt woman) are benign. In pregnant women, ahout 70% of hen@ lesions are the typical lesions seen in all women (eg, fibroadenomds), and 30% are benign conditions unique to pregnancy (such as lobular hyprrplasia, or localized breast infarcts). I’-’15 Although intlammatory carcinoma of the breast is no more common during pregnancy than at other times, the condition i< sometimes misdiagnosed as a breast abscess.” Incision and drainage cd a suspected breast abscess should not be performed without doing a biopsy of the abscess wall. If a breast dbscesh does not respond to antibiotic treatment, proceed tcj surgery. Prcllonged delays from hreast mass recognition to mammary Lancer diagnosis in pregnancy pose a significant prohl~tn.“~‘4 Difficulty in palpating lumps and a reluctance to perf&m i-1biopsy hoth contribute. Biopsy cm be performed wirh the patient under local anesthesia. Hemostasis is critical; the increased vascularity of the puerperal hreast predisposes to bleedmg and hematoma f~~rmation. If needed, general anesthesia is also :Icceptable. Byrd and c
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occur if surgery is performed while breast fcedmg continsome women prefer to accept this risk rather than cease breast feeding.”

ues;

Treatment Surgical treatment of breast cancer should proceed during pregnancy as it would in other women of reproductive age.j! Generally, modified radical mastectc)tny under general anesthesia will be required for early-stage breast cancer and shoulcl prciceed without delay. Allowing the pregnancy to progress to fetal viability prior to etnharkmg on a surgical cure has not been proved beneficial to mother or fetus. ii,‘4 In some instances, when cancer is diagnosed near term, delivery mdy be accomplished prior to surgery. In rare cases, a locally aggressive malignancy diagnosed very early in pregnancy and requiring radiation therapy may justify therapeutic abortinn; however, therapeutic ,IhL)rtlon is rarely advised.” Early recommendations strongly in favor of termination cd pregnancy were based upon the assumption that gestational breast cancer was uniformly f:ltal.“‘.” Stage-forstage, current studies show equivalent survival when women who develop breast cancer during pregnancy are compared with the general population of breast cancer patients.‘5,ih The mortality of breast cancer during prqnallcy is related to delay in diagnosis and treatment. Appn~ximately 75% of women diagnosed during pregnancy will have positive modes (conrrasted with 37% in the general population).” There may be a slightly increased incidence of tnulticentricity and bilateral breast cancers (7 of 6’3 women, m ,I series from Memorial Hospital)” in women with gestational breast cancer. These series are small, and dat,l are Inconclusive. The general rule is to treat the cancer and all~)w rile pregnancy to proceed. When contemplating pregnancy tetminatl~m, other considerations include prognosis of the malignancy ;and the ability of patient and family to cope with dual demands of a newhorn infant and possible ongoing therapy for malignancy or even maternal death. Staging should he individualized m the preqt;tnt patient to maximize useful information and mintmix fetal risk. Staging studies, such as head computed tomography or tnagnetic resonance imaging can be pert~Nmed with minimal fetal exposure to radiation; however, these are usually postponed until after delivery. Yield on bone scan ii particularly low, and this test can also be postponed. Hortnone-receptor status of the tumor biopsy is often evaiuated, as in nonpregnant patients. The significance and reliability of estrogenand pr(‘gesten)nc-receptor protein arlalysis arc’ not clear. It is thought that s;lturation of receptor> by circulating pregnancy-related horm
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in pregnancy when the uterus is high and close to the breast. A certain amount of this radiation exposure results from internal scatter from the mother’s body tissues and cannot be diminished by external shielding. Generally, radiation treatment should be postponed until after delivery.‘6,39 This does not necessarily render breast-conservation surgery impracticable, but there are few data on the effect of delay of radiation therapy after lumpectomy during pregnancy. Most would advise modified radical mastectomy to avoid the problems of radiation therapy during pregnancy, with risk to the fetus, or postponement of therapy (after lumpectomy), with risk to the mother. All chemotherapeutic agents are potentially teratogenic; however, the observed incidence of malformations is small. Most studies involve drugs used in treating leukemia; little is known about drugs used for treating breast cancer.40-42 The classic teratogenic period is from day 3 1 to 7 1 of human gestation, but low birth weight and prematurity or known complications of chemotherapy can occur in any trimester.40~41,43 Women considered low-risk (stage I or II) can begin chemotherapy after delivery. Sometimes early delivery, after documenting fetal lung maturation, is desirable to minimize delay. In general, the effect of chemotherapy on the fetus during the second and third trimesters is less pronounced than therapy initiated during the first trimester. The use of systemic chemotherapy to treat advanced breast cancer, in the second trimester, with successful fetal outcome has been reported.44 Before administering chemotherapy to such patients, however, they must be willing to accept the risks of premature delivery as a consequence of treatment.

Pregnancy After Treatment for Breast Cancer Patients who are clinically free of disease are not adversely affected by pregnancy.3,33,39*45,46There is no reason to recommend therapeutic abortion if a woman becomes pregnant after successful treatment of breast cancer. Patients contemplating future childbearing may be given oral contraceptives without increasing the risk of cancer recurrence.47

SUMMARY In summary, the majority of breast lesions encountered during pregnancy are benign; however, 20% of breast masses prove to be malignant. Physiologic changes of pregnancy make evaluation of the breast difficult, and baseline and serial examinations are critical. Mass lesions should prompt an immediate biopsy. A significantly higher percentage of women diagnosed with breast cancer during pregnancy are node positive. The mortality of breast cancer during pregnancy is related to delay. When compared stage-for-stage with nonpregnant controls, the prognosis is similar. As a general rule, treat the cancer surgically with a modified radical mastectomy and allow the pregnancy to progress. Minimize fetal exposure to radiation. Pregnancy after successful treatment of breast cancer does not adversely affect outcome and there is no reason to recommend therapeutic abortion.

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2. McNeilly AS, Robinson ICA, Houston MJ, Howie PW. Release of oxytocin and prolactin in response to suckling. BMJ. 1983;286: 257-259. 3. Nugent l’, O’Connell TX. Breast cancer in pregnancy. Arch Surg. 1985;120:1221-1224. 4. Olsen CG, Gordon RE Jr. Breast disorders in nursing mothers. Am Fam Physician. 1990;41:1509-1516. 5. Thomsen AC, Fspersen T, Maigaard S. Course and treatment of milk stasis, noninfectious inflammation of the breast, and infectious mastitis in nursing women. Am J Obstet Gynecol. 1984;149:492495. 6. Isada IB, Grossman JH III. Perinatal infections. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics Normal and Probkm Pregnancies. 2nd ed. New York: Churchill Livingstone; 1991:1284-1289. 7. Neibyl J, Spence M, Parmely T. Sporadic (nonepidemic) puerperal mastitis. J Reprod Med. 1978;20:97-100. 8. Marshall B, Hepper J, Zirbel C. Sporadic puerperal mastitis: an infection that need not interrupt lactation. JAMA. 1975;233:1377-1379. 9. Dixon JM. Repeated aspiration of breast abscesses in lactating women. BMJ. 1988;297:1517-1518. 10. Eschenbach DA. Acute postpartum infections. Emerg Med Clin North Am. 1985;3:87-115. 11. Winker JM. Galactocele of the breast. Am J Surg. 1964;108: 357-360. 12. Sheldon TA, Parker LM, Cady B. Special therapeutic problems. In: Harris JR, Hellman S, Henderson IC, Kinne DW, eds. Breast Diseases. Philadelphia: JB Lippincott; 1987:563-63 1. 13. Novotny DB, Maygarden SJ, Shermer RW, Frable WJ. Fine needle aspiration of benign and malignant breast masses associated with pregnancy. Acta Cytol. 1991;35:67&686. 14. Hall FM. Galactocele: three distinctive radiographic appearances. Radiology. 1986;160:852-853. 15. Page DL, Simpson JF. Benign, high-risk, and premalignant lesions of the mamma. In: Bland KI, Copeland EM, eds. The Breast: Compehensiue Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1991:113-134. 16. Lucy JJ. Spontaneous infarction of the breast. J Clin Pathol. 1975; 28:937-943. 17. Robitaille Y, Seemayer JA, Thelmo WL, Cumberlidge MC. Infarction of the mammary region mimicking carcinoma of the breast. Cancer. 197+33:1183-l 189. 18. Scott-Conner CEH, Powers C, Subramony C, Didlake RH. The changing clinical picture of mammary hamartoma. Am J Surg. 1993; 165:20&212. 19. Tchabo JG, Stay EJ. Gravidic macromastia: case report. AmJ Obstet Gynecol. 1989;160:8&89. 20. Gargan TJ, Goldwyn RM. Gigantomastia complicating pregnancy. Plast Reconsa Surg. 1987;80:121-124. 21. Stavrides S, Hacking A, Xltman A, et al. Gigantomastia in pregnancy. Br J Surg. 1987;74:585-586. 22. Eben F, Cameron MD, Lowy C. Successful treatment of mammary hyperplasia in pregnancy with bromocriptine. Br J Obstet Gynaecol. 1993;100:95-96. 23. Van Heerden JA, Gharib H, Jackson IT. Pseudohyper-parathyroidism secondary to gigantic mammary hypertrophy. Arch Surg. 198&123X?-82. 24. Lafreniere R. Bloody nipple discharge during pregnancy: a rationale for conservative treatment. J Surg Oncol. 1990;43:228-230. 25. Neifert M. Breastfeeding after breast surgical procedure or breast cancer. NAACOGS Chn Issu Perinat. Womens Health Nurs. 1992;3: 673-682. 26. Anderson JM. Mammary cancer and pregnancy. BMJ. 1979;l: 1124-1127. 27. Wallack MK, Wolf JA Jr., Bedwinek J, et al. Gestational carcinoma of the female breast. Curr Probi Cancer. 1983;7:1-58. I mcenti E Carcinoma of the breast 28. Applewhite RR, Smith LR, D’V associated with pregnancy and lactation. Am Surg. 1973;39:101-104. 29. Haagensen CD. Carcinoma of the breast in pregnancy. In:

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Haagensen CD, ed. Disease of the Breast. 2nd ed. Philadelphia: WB Saunders; 1971:66O-664. 30. Donegan WL. Mammary carcinoma and pregnancy. Major Prob Clin Surg. 1967;5:17&178. 31. Byrd BF, Bayer DS, Robertson JC, et al. Treatment of breast tumors associated with pregnancy and lactation. Ann Surg. 1962;155: 940-947. 32. Gallenberg MM, Loprinzi CL. Breast cancer and pregnancy. Semin Oncol. 1989;16:369-376. 33. Donegan WL. Cancer and pregnancy. Cancer. 1983;33:194-214. 34. Ribeiro GG, Palmer MK. Breast carcinoma associated with preg nancy: a clinician’s dilemma. Bw. 1977;2:1524-1527. 35. King RM, Welch JS, Marten JK, Coulam CB. Carcinoma of the breast associated with pregnancy. Surg Grnecol Obstet. 1985;160: 228-232. 36. Waalen J. Pregnancy poses tough questions for cancer treatment. J Natl Cancer Inst. 1991;83:9OO-902. 37. Ribeiro G, Jones DA, Jones M. Carcinoma of the breast associated with pregnancy. Br J Surg. 1986;73:607-609. 38. Bunkers ML, Peters MV. Breast cancer associated with pregnancy and lactation. Am J Obstet Gynecol. 1983;146:938-941. 39. Denoix P Treatment of malignant breast tumors. Recent Results Cancer Res. 1970;31:81-84.

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40. Schapira DV, Chudley AE. Successful pregnancy following continuous treatment with combination chemotherapy before conception and throughout pregnancy. Cancer. 1984;54:800-803. 41. Jones SE. Management of breast cancer in the pregnant patient. Contemp Oncol. 1992:19-24. 42. A&s A, Niz J. Long-term follow-up of children born to mothers with acute leukemia during pregnancy. Med Pediaa Oncol. 1988;16: 3-6. 43. Schwartz PE. Cancer in pregnancy. In: Reece AE, Hobbins JC, Mahoney MJ, Petrie RH, eds. Medicine of the Mother and Femur. Philadelphia: JB Lippincott; 1992:1257-1281. 44. Willemese PHB, vd Sijde R, Sleijfer DT. Combination chemotherapy and radiation for stage IV breast cancer during pregnancy. Gynecol Oncol. 1990;36:281-284. 45. Danforth DN Jr. How subsequent pregnancy affects outcome in women with a prior breast cancer. Oncoloa. 1991;5:23-30. 46. Harvey JC, Rosen PP, Ashikari R, et al. The effect of pregnancy on the prognosis of carcinoma of the breast following radical mastectomy. Surg Gynecol Obstet. 1981;153:723-725. 47. Bush H, McCredie ]A. Carcinoma of the breast during pregnancy and lactation. In: Allen HH, Nisker JA, eds. Cancer in Pregnancy. Mt. Kisco, NY: Futura Publishing; 1986:91-98.

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