Updated November 2004
Since breast cancer is the most common tumour occurring in women during the reproductive years, carcinoma of the breast in pregnancy does occur and presents special management problems. It is, fortunately, relatively unusual and each case deserves consideration on its own merits with referral to multidisciplinary conference. It is extremely important to assess the potential for cure in an individual patient. The welfare of the patient and the fetus needs to be evaluated.
New suspicious localized breast masses should undergo evaluation with mammography and ultrasound. Core biopsy should be carried out if indicated. Mammography can be performed utilizing abdominal and pelvic shielding. Breast MRI cannot be carried out due to the need for gadolinium. If metastatic staging is indicated, consideration should be given for chest radiograph with fetal protection, ultrasound assessment for liver lesions, and non-contrast MRI of the thoracic and lumbar spine.
First Twelve Weeks
Surgery can be carried out safely during pregnancy. However, consideration may be given for therapeutic abortion to allow for timely treatment and should be considered on an individual basis. In this scenario, the treatment of the malignancy will then proceed as in the non-pregnant state. Patients who continue with the pregnancy commonly undergo mastectomy. Breast conserving therapy is possible if radiation therapy can safely be deferred to the post-partum period. Axillary staging should be carried out (see below) in accordance with recommendations in the non-pregnant state.
No adjuvant radiation therapy should be given during pregnancy. Chemotherapy with AC chemo has been given in this situation, but is avoided if possible, unless the risks of withholding chemo outweighed the risks to the fetus. Referral is recommended to assess the need for further treatment after the baby has been delivered.
Twelve to Twenty-eight Weeks
During this interval the breast cancer can be adequately treated surgically without terminating pregnancy. Patients may undergo breast conserving surgery or mastectomy. Axillary staging should be carried out. (see below). Adjuvant radiotherapy is contraindicated during pregnancy. The risk of recurrence should be estimated based on the pathology of the tumour. If the risk of relapse is high then adjuvant chemotherapy may be given. Cyclophosphamide and doxorubicin with or without 5-fluorouracil is the preferred combination during pregnancy. Epirubicin and taxanes should be avoided. Tamoxifen exposure in the first and second trimesters may be associated with genitourinary abnormalities and therefore should be avoided. Referral of these patients for assessment is recommended.
Twenty-eight Weeks to Term
Maturity of the fetus should be assessed. Consideration should be given to inducing labour as soon as obstetric advice indicates that the fetus is viable. Surgical treatment (breast conserving surgery or mastectomy +/- axillary staging, see below) should be carried out. As soon as the fetus has been delivered the patient should receive additional treatment as for the non-pregnant state. Chemotherapy may be given during pregnancy (see above), but in most circumstances is delayed until after delivery.
Axillary Staging in Pregnancy
Radiolabelled technetium colloid appear to be safe in pregnancy and sentinel lymph node biopsy may be carried out using technetium-99 with avoidance of blue dye. However, breast lymphatic drainage may be altered in pregnancy and the sensitivity and specificity of SLNB have not been established in this setting. Safety data were derived from limited case reports and series. Thus, there is insufficient data for a strong recommendation for its use during pregnancy and should be discussed on an individual basis.
Lactation
When a carcinoma arises during lactation, lactation should be terminated and therapy appropriate for the treatment of the malignancy instituted.
Patients with advanced disease pose a special problem. In the early weeks of pregnancy, consideration has to be given to termination of the pregnancy. If the patient is in the second trimester and is still hoping to deliver a viable child then chemotherapy with drugs least likely to harm the fetus may be considered (see above).
Referral to BC Cancer is recommended. Radiotherapy is contra-indicated except in exceptional circumstances.
Updated: February 2016
Cancer of the male breast is uncommon, about one percent of all breast cancers. Investigation of breast cancer in the male is identical to that of the female patient, including mammography as an initial investigation.
Because the male breast is very small, mastectomy has commonly been carried out. Recommendations for axillary staging in the male remain the same as that for female patients. Pathologic assessment for tumour characteristics and hormone receptor status is identical to that in females. Local resection (i.e. lumpectomy) combined with radiation may be possible and should be discussed at multidisciplinary conference. The
indications for post mastectomy radiation for males are the same as those for females (i.e. in those with T3/T4 or node-positive disease).
There are no series of male patients, which have been adequately studied in regard to adjuvant systemic therapy. However, experience demonstrates that the clinical behaviour of male and female breast cancers are very similar. Because of this, adjuvant hormonal or chemotherapeutic recommendations are the same, stage-for-stage, as for a woman of the same age. The role of aromatase inhibitors and fulvestrant in males has not been established. Orchiectomy or LHRH may provide a response after progression on tamoxifen in the metastatic setting.
Breast cancer in young women (less than 40 years of age) requires additional consideration for issues specific to this patient population. Multidisciplinary care is strongly recommended.
In general, overall management should not significantly differ in terms of surgical options and adjuvant treatment recommendations when compared to women > 40 years of age. Of note, neoadjuvant endocrine therapy is typically not recommended for young women and aromatase inhibitors are not recommended in pre-menopausal women.
Specific considerations:
- Pregnancy-associated breast cancer
- Fertility Preservation
- a. All young women with a breast cancer diagnosis and the desire for future children should be referred to a fertility specialist prior to the initiation of any therapies
- b. Options for fertility preservation include:
- i. GnRH analogues during chemotherapy
- ii. Oocyte/embryo cryopreservation
- iii. Ovarian tissue freezing
- Pregnancy after Breast Cancer
- a. Women should complete the recommended length of their treatments before trying to conceive
- b. The risk of relapse due to stopping treatment prematurely should be discussed and weighed against patient’s desire for children and risk of delaying pregnancy.
- c. A treatment free interval after chemotherapy and/or endocrine therapy should be recommended to allow for potentially harmful agents to be eliminated from the system before pregnancy. Patients should communicate with their physicians early on if they are planning to get pregnant to allow for a coordinated plan.
- d. This issue is discussed more fully in section 7.2.5 (LINK to this section)
- Contraception before, during and after treatment
- a. Contraception is strongly recommended during treatment for all young women with breast cancer, as amenorrheic women may still be fertile, and pregnancy is generally a contraindication to adjuvant treatment.
- Effect of Surgery and Adjuvant therapies on Lactation and Breast-feeding
- a. Breast-feeding after treatment can still be completed
- b. Milk production may be reduced from a breast that has undergone surgery and radiation. Feeding from the opposite breast should be encouraged. Breast-feeding after bilateral mastectomies will not be possible.
- c. Women should be off any chemotherapy or endocrine medications during breast-feeding.
- Desire for Breast Reconstruction
- a. A higher proportion of young women opt for breast reconstruction if they are undergoing mastectomy. Referral to a plastic surgeon is recommended for either immediate or delayed reconstruction.
- Side effects of adjuvant therapies to address:
- a. Pre-mature menopause
- b. Lymphedema
- c. Bone Health
- d. Sexual function and identity
- e. Cognitive impairment
- Genetics
- a. A majority of young women with breast cancer qualify for genetic counselling and subsequent genetic testing. Referral is recommended.
- Psychosocial support
- a. Additional supports may be required in terms of financial support due to inability to work, counselling for relationships with spouse and children and community supports for childcare, etc. Referral to a counsellor or support group is recommended.
- Clinical trials/Research Studies
- a. An increasing number of studies are being completed for young women with breast cancer. Identification of appropriate trials or studies for patients should be attempted
References
- Cardoso F, Loibl S, Pagani O, Graziottin A, Panizza P, Martincich L, Gentilini O, Peccatori F, Fourquet A, Delaloge S, Marotti L, Penault-Llorca F, Kotti-Kitromilidou A, Rodger A, Harbeck N. The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer. 2012 October 2012.
https://www.eusoma.org/en/recommendations/other-guidelines/the-european-society-of-breast-cancer-specialists-recommendations-for-the-management-of-young-women-with-breast-cancer/1-396-1-
- Partridge AH, Pagani O, Abulkhair O, Aebi S, Amant F, Azim HA Jr, Costa A, Delaloge S, Freilich G, Gentilini OD, Harbeck N, Kelly CM, Loibl S, Meirow D, Peccatori F, Kaufmann B, Cardoso F. First international consensus guidelines for breast cancer in young women (BCY1). Breast. 2014 Jun;23(3):209-20. doi: 10.1016/j.breast.2014.03.011. Epub 2014 Apr 24. http://www.thebreastonline.com/article/S0960-9776(14)00055-1/pdf
There are additional considerations when managing older patients. Many older patients have comorbidities that increase their risk from surgical procedures or from systemic therapy,and may have contraindications to radiotherapy. As a result of these factors, older patients are less likely to be offered standard treatment for breast cancer, which may negatively affect survival.1
Randomised trials of adjuvant radiotherapy after lumpectomy in older women with Stage 1 (T1N0M0), ER + breast cancer undergoing a 5-year course of tamoxifen have shown that radiation therapy is associated with the same relative reduction in local recurrence as in younger women, reducing the risk of local recurrence by 2/3 – ¾. In this population, however, the baseline local recurrence risk is significantly lower, e.g. 6-10% at 10 years, resulting in a much lower absolute benefit. In this cohort, in women with very low-risk tumours, breast conserving surgery and hormonal therapy, without adjuvant radiotherapy, is a viable
option that likely has similar survival.
2,3,4,5
Many randomized chemotherapy studies excluded older patients, which makes it difficult to extrapolate what the benefit is in this cohort. Given that older patients may not tolerate chemotherapy as well as younger patients due to limited bone marrow reserve and comorbidities, careful consideration must be given to weigh the risks and benefits of chemotherapy. Hormonal therapy alone often provides excellent results in this cohort.
Multidisciplinary discussion for the management of these patients is encouraged.
References
- Hans Wildiers, Ian Kunkler, Laura Biganzoli, et al. Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology. Lancet Oncology Vol 8 December 2007
- Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 2004;351: 971–77.
- Hughes, Kevin S.; Schnaper, Lauren A.; Bellon, Jennifer R.; Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. Journal of Clinical Oncology (2013), 31(19), 2382-2387
- Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, et al. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):963-70.
- Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM; PRIME II investigators. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015 Mar;16(3):266-73. doi: 10.1016/S1470-2045(14)71221-5. Epub 2015 Jan 28
Paget’s Disease of the Breast
Management of Paget disease of the breast is discussed in
Section 6.2 "In Situ Disease". In summary, women with Paget’s disease of the nipple-areolar complex should be thoroughly investigated as the majority of patients have an associated in situ or invasive breast cancer that is managed in accordance to the in situ/invasive breast cancer component, as well as therapy directed for the treatment of Paget disease.
Variants of Invasive Breast Cancer
There are a number of pathologic variants of invasive breast cancer that are treated the same way as described above for more common invasive ductal or lobular breast cancer, not otherwise specified (NOS).
Tubular, mucinous (colloid), cribriform, and medullary carcinomas are all variants of invasive ductal carcinoma, that generally hold a more favourable prognosis. Micropapillary carcinomas tend to be more aggressive, and are more frequently associated with axillary nodal metastases. As with more common invasive ductal carcinomas NOS, patients with any of these pathologies should be managed initially surgically, with appropriate nodal staging and adjuvant therapy as described above.
Metaplastic tumours
Metaplastic tumours are tumours that are comprised of more than one histology, specifically high-grade invasive ductal adenocarcinoma plus either sarcomatous and/or non-glandular epithelial components (e.g. squamous cell carcinoma). These tumours may metastasize through the lymphatic system, and therefore require axillary sampling (e.g. with sentinel node biopsy). These tumours are typically estrogen and progesterone receptor negative and her-2-neu negative, and appear to be more aggressive than common invasive ductal carcinomas. It is possible that they do not respond as well as typical invasive ductal carcinomas to standard adjuvant therapy. In spite of this, patients with this histology should be managed with mastectomy or breast conserving surgery with axillary staging, plus adjuvant radiation and systemic therapy as described above for more common invasive ductal carcinomas, NOS.
Phyllodes Tumours of Breast (Cystosarcoma Phyllodes)
Updated February 2017
These uncommon sarcomas of the female breast arise from the stromal elements. Clinically and on imaging, they may appear very similar to fibroadenomas, although large size and rapid development or growth of the lesion should raise clinical suspicion. Histologically they may be categorized as benign, borderline, or malignant. Adenocarcinoma may co-exist and therefore pathology review of these tumours is recommended. A phyllodes tumour should be suspected if a fibroadenoma is "recurrent."
The mainstay of treatment of Phyllodes tumours is surgical excision.1,2,3,4 Specimens should be inked so their margins can be assessed for involvement by tumour. If the lesion is deep in the breast, the excision must include fascia. NCCN currently recommends a surgical procedure with the intention of obtaining a 1 cm margin.
More recent studies
4,5,6,7 are showing little difference between closer margins and widely clear margins for malignant, borderline, and benign tumours and this has also been found when reviewing provincial data.
8 Factors that suggest an increased recurrence rate in recent studies include tumour on inked margin, size of tumour, grade of tumour, stromal overgrowth, infiltrating borders, heterologous sarcomatous differentiation, malignant epithelial transformation and increased mitoses.4,5,6,7,8 All of these factors should be considered in assessment of adequate margins. A pathology review and
referral to BC Cancer may be helpful.
As lymph node metastases are rare, in the absence of adenocarcinoma elements, axillary node dissection is not recommended. Local recurrences may predict for development of metastases even in patients with "benign" disease. Metastases are generally to lung, although bone and liver involvement may occur.
Patients with more aggressive histology may be offered radiation therapy to improve local control rates. There is no known role for chemotherapy in the adjuvant setting.
References
- Barrio A, Clark B, Goldberg J, et al. Clinicopathologic features and long term outcomes of 293 phyllodes tumors of the breast. Ann Surg Oncol 2007;14:2961-2970.
- Guillot E, Couturanud B, Reyal F et al. Management of Phyllodes breast tumors. Breast J 2011;17:129-137.
- Kim S, Kim Y, Kim d, et al. Analysis of phyllodes tumor recurrence according to the histologic grade. Breast Cancer Res Treat. 2013;14:353-63.
- Onkendi E, Jimenez R, Spears G, et al. Surgical Treatment of borderline and malignant phyllodes tumors: the effect of the extent of resection and tumor characteristics on patient outcome. Ann Surg Oncol 2014; 21:3304-3309.
- Jang J, Choi M, Lee S, et al. Clinicopathologic Risk Factors for the local recurrence of Phyllodes tumor of the breast. Ann Surg Oncol 2012; 19: 2612-2617
- Kaveh Borhani-Khomani MS, Maj-Lis Møller Talman MD, Niels Kroman MD, DMSc, Tove Filtenborg Tvedskov MD, PhD Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors: A Danish Population-Based Retrospective Study. Breast Oncology Volume 23, Issue 5 / May , 2016
- Yom C, Han W, Kim S et al Reappraisal of Conventional Risk Stratification for Local Recurrence Based on Clinical Outcomes in 285 resected Phyllodes Tumors of the breast. Ann Surg Oncol (201) 22:2912-2918.
- Rodrigues MF, Truong PT, McKevitt EC, Weir LM, Knowling MA, Wai ES. Phyllodes tumours of the breast: the British Columbia Cancer Agency experience. In Press, Cancer Radiotherapie
