Current surgical management of breast cancer

ABSTRACT: Definitive treatment of breast cancer is surgical. Typically, the primary tumor is excised and axillary nodes are removed for staging. The decision on optimal treatment for the breast can be challenging for the clinician and the patient because of the wide variety of surgical options, including breast conserving surgery and mastectomy with or without immediate or delayed breast reconstruction. Surgical management of the axilla for clinically node-negative and node-positive patients has progressed significantly over time. Sentinel node biopsy is now recommended for many clinical scenarios that would have previously required axillary node dissection. As optimal management of breast cancer is becoming more complex, many patients may benefit from early multidisciplinary review to aid in clinical decision making and to develop a patient specific treatment strategy. Current surgical management of breast cancer in British Columbia is based on consensus recommendations from the Breast Tumour Group of the BC Cancer Surgical Oncology Network.


Evolving indications for radiotherapy and systemic therapy along with less-aggressive surgical techniques have changed the way breast malignancies are managed.


Over the years, surgery for breast cancer has become less invasive in both the breast and axilla.[1-4] Surgical techniques have advanced to provide better cosmesis in breast conservation and also in breast reconstruction for woman who require mastectomy.[5,6] Because definitive treatment of breast malignancy continues to be surgical, the surgeon remains a crucial member of the multidisciplinary team caring for breast cancer patients. Women faced with this diagnosis often have options on how best to manage the breast and axilla in both invasive and in situ malignancy. Decision making surrounds the extent of mastectomy for immediate breast reconstruction, the use of neoadjuvant therapy, and breast cancer at extremes of age. These can be challenging decisions and often require multidisciplinary care to guide best treatment.

Prior to surgery
To diagnose breast cancer, a patient will require a detailed history, physical examination, breast imaging, and tissue biopsy to confirm and identify the extent of disease. Bilateral diagnostic mammogram is the only required imaging. Breast or axillary ultrasound may be needed to rule out multifocal disease or regional metastasis.[7,8] Bilateral breast MRI is not recommended in the routine assessment of unilateral breast cancer. MRI has been shown to lead to additional investigations that delay surgery and result in overtreatment with no improvement in survival, recurrence, or repeat surgery rates.[9]

The use of staging investigations to identify distant disease prior to surgery is not recommended unless patients have symptoms suggestive of metastatic disease or have advanced breast cancer (i.e., stage III). Routine use of bone scan and chest or abdominal imaging for early cancer is discouraged as these investigations have a low yield, can delay treatment, and can cause anxiety.[7,8,10]

Breast conserving surgery
Breast conserving surgery (BCS) is the recommended approach for most patients with early stage breast cancer. BCS includes local resection of breast tissue (known as lumpectomy, partial mastectomy, or segmental mastectomy) and is typically followed by radiotherapy. BCS combined with radiotherapy has been shown in multiple randomized control studies to be equivalent to mastectomy in terms of survival in patients with early stage disease[2,11,12] and new studies suggest a potential survival advantage for BCS and radiotherapy when compared to mastectomy.[13] BCS should be offered if the tumor-to-breast ratio would give a reasonable cosmetic outcome following the procedure. If the tumor is too large to allow for a reasonable cosmetic result, altering the surgical technique or the timing of systemic treatment may make the patient a candidate for BCS. Oncoplastic approaches that combine breast conservation and plastic surgery techniques have developed to allow BCS in larger tumors.[5] Another option for some women motivated to undergo breast conservation is the use of neoadjuvant therapy (NAT), which may shrink the tumor enough to allow BCS. These strategies have permitted more women with larger tumors to achieve acceptable oncologic and cosmetic outcomes after BCS.[5,14,15]

The main challenge presented by BCS is the need for reoperation because of positive margins and a slight increased risk of local in-breast recurrence when BCS and radiotherapy are compared to mastectomy.[2,11] Patients with positive margins should be evaluated for further surgery. Patients with negative margins (no ink on tumor) do not require any additional surgery as reoperation for close margins (less than 2 mm) does not significantly improve their outcome.[16]

Unnecessary reoperation has increased risk of complications, can delay adjuvant treatments, and can be costly and detrimental to cosmesis.[17,18] Reoperation occurs in 20% to 30% of BCS cases.[19] Local in-breast recurrence after BCS and radiation occurs in less than 10% of women and is usually treated with mastectomy.[20] Again, despite increased local recurrence risk, the survival outcomes for BCS with radiotherapy are at least equivalent to mastectomy.[2]

Contraindications for BCS include multicentric disease, unfavorable tumor-to-breast ratio, previous radiation therapy to the area, and disease processes that limit the use of radiation therapy.[21] Some woman can avoid radiation if they have small tumors with favorable biology that would confer a reduced risk of recurrence. Patients in remote communities who have traditionally opted for mastectomy to avoid travel for radiotherapy might be eligible for BCS alone in some circumstances. If this is considered, a preoperative discussion with a radiation oncologist is recommended.[22]

Mastectomy
Breast cancer that cannot be treated adequately with breast conserving surgery will require mastectomy. Mastectomy is recommended for patients when radiotherapy is contraindicated or there is a desire to avoid radiotherapy. Mastectomy is also recommended for patients who would have a poor cosmetic outcome with BCS, and those with multicentric disease or invasive cancer associated with diffuse, extensive ductal carcinoma in situ (DCIS). Mastectomy should also be considered in those who continue to have positive margins with invasive disease after multiple attempts at BCS.[20] Women who choose mastectomy in order to avoid radiation treatment must be counseled that the indications for postmastectomy radiotherapy are increasing and the additional benefit of radiotherapy is not always known at the time of preoperative consultation because it is dependent on final pathology.[23] Mastectomy offers no survival advantage when compared to BCS with radiation therapy and can still result in local recurrence on the chest wall of 2% to 5%.[2] Aside from the particular situations requiring mastectomy described above, BCS with radiation therapy is the standard for patients with early stage breast cancer.[12]

Breast reconstruction
Many women consider breast reconstruction after mastectomy. Immediate breast reconstruction (IBR) can be performed at the time of mastectomy or delayed breast reconstruction can be undertaken afterwards. Options for breast reconstruction include autologous tissue or implant reconstruction. If IBR is performed, skin sparing mastectomy or nipple sparing mastectomy techniques are possible. There are specific oncologic and patient factors that will influence surgical decision making regarding the extent of mastectomy and the ability to offer skin or nipple preservation. Skin sparing mastectomy with IBR has shown no increased risk of recurrence. Immediate breast reconstruction is not recommended for patients who are morbidly obese or current smokers, or patients with inflammatory breast cancer or a cancer that will not permit skin sparing techniques with negative margins. Many women who are not candidates for IBR can consider delayed reconstruction when their cancer treatments are completed. It is now considered the standard of care for every woman requiring or choosing a mastectomy for treatment of breast cancer to be made aware of her breast reconstruction options (immediate and delayed) and have access to consultation with a plastic surgeon (either at diagnosis or into survivorship).[6,24]

For women who require mastectomy and are candidates for IBR, a nipple and/or areola sparing technique may also be a viable option. The breast oncologic surgeon and the reconstructive surgeon will make that determination together based on tumor factors (small tumors located more than 2 cm from the nipple without extensive malignant type calcifications suggesting DCIS) and patient factors (small to moderate breast size with minimal ptosis). A nipple margin (core) should be taken when a nipple sparing mastectomy is performed.[20,25] Nipple sparing mastectomy patients are at risk of nipple necrosis (5.9%) and local (including nipple/areola) cancer recurrence (2.38%).[25]

Contralateral prophylactic mastectomy
Patients who require a mastectomy to treat unilateral breast cancer often inquire about the risk of a contralateral breast cancer (CBC) and the possibility of contralateral prophylactic mastectomy (CPM). A detailed medical and family history is required to assess these patients.

For the average woman, the risk of CBC is less than 0.7% per year. CBC is more common in higher risk patients (e.g., women who are BRCA mutation carriers) and the risk is reduced by CPM but not eliminated completely. Systemic treatments also reduce the risk of CBC.

Rates of contralateral prophylactic mastectomy are rising at more than 1% per year[26] and have been known to almost double the risk of complications after surgery. CPM in an average risk woman does not improve cancer outcomes.[27] As such, CPM is not recommended for women with unilateral breast cancer, but may be considered in cases where a patient is at moderate risk of CBC because of very young age, a strong family history of breast cancer, other high-risk features such as atypical ductal hyperplasia or lobular carcinoma in situ, or when asymmetry after unilateral mastectomy (with or without breast reconstruction) is a concern. High-risk unilateral breast cancer patients (e.g., genetic mutation carriers, those with a history of mantle field radiation) should be counseled on the risk of CBC, and CPM may be recommended.[27]

A Canadian expert consensus statement on this issue is a work in progress. Other groups, including the American Society of Breast Surgeons[27] and Choosing Wisely,[28] have consensus statements discouraging the routine use of CPM.

Staging
Axillary staging provides important prognostic information, guides adjuvant therapy decisions, and can improve regional control for some patients with invasive breast cancer. Traditionally, dissection of level I and II axillary lymph nodes has been the standard of care for all patients with invasive breast cancer. Axillary lymph node dissection (ALND) has now been replaced by sentinel lymph node biopsy (SLNB) for most patients with clinically node-negative breast cancer.[3,29] Sentinel lymph node biopsy is associated with less morbidity[30] and when compared with ALND has similar staging accuracy and oncologic outcomes in early breast cancer.[3] SLNB should be offered to all eligible patients. As the role of axillary staging and the extent of axillary surgery continue to evolve, multidisciplinary conferences can be helpful in making the best decision for the patient. Practice guidelines (Table) have been developed to help guide decision making for ALND.[29,31]

SLNB is adequate axillary surgery for node-negative patients,[3] for many women with low volume nodal meta-stasis (one or two positive nodes), and for patients with lower risk disease who take systemic treatment.[31] ALND is generally recommended for patients with three or more positive sentinel nodes or for those at high risk for gross residual nodal disease after SLNB.[31] ALND in this situation may improve regional control but has no proven survival advantage.[1] Patients with node-positive breast cancer will often be offered radiotherapy regardless of the degree of nodal burden to reduce regional recurrence and improve survival.[32]

For women with positive results on SLNB, radiotherapy gives local control comparable to that achieved by ALND and results in less morbidity.[33] Women who require both ALND and regional radiotherapy are at the highest risk for lymphedema. In the absence of a proven survival advantage for ALND, and significant risk for patients who may require regional radiotherapy and ALND, thoughtful multidisciplinary decision making regarding the best management of the axilla should be undertaken prior to proceeding with ALND.

Ductal carcinoma in situ
Ductal carcinoma in situ is a nonobligate precursor of invasive breast cancer that is being diagnosed more often with breast cancer screening and advances in breast imaging. DCIS currently represents 20% to 25% of all breast malignancies. At present, all patients with DCIS are offered treatment. Patients with DCIS may be treated with breast conserving surgery or mastectomy.[34] Skin sparing mastectomy and immediate breast reconstruction are appropriate for most patients who require mastectomy for DCIS, although nipple sparing approaches are still controversial. All management strategies are associated with survival exceeding 98%.[35]

Ideally, DCIS is removed with a wide margin as this approach is associated with less risk of in-breast tumor recurrence. The margin recommended in DCIS (2 mm) is wider than that recommended in invasive breast cancer (no ink on tumor) because of the growth pattern of DCIS (skip lesions) and the lack of routine systemic treatment in these patients. Margin widths greater than 2 mm do not confer a significant benefit in local control.36 Currently, adjuvant radiotherapy is recommended for women with DCIS greater than 1 cm who are treated with BCS to reduce local recurrence. Women with well-differentiated DCIS that is less than 1 cm with wide excision may be considered for management by wide excision alone.[37]

Axillary staging is not routinely recommended for patients with pure DCIS because the risk of axillary nodal involvement is less than 1%. Sentinel lymph node biopsy is advised for patients undergoing mastectomy for DCIS29 because of the possibility of an invasive component in the final surgical specimen. SLNB is also recommended for patients with DCIS with microinvasion.[38] The risk that DCIS will be upstaged to invasive cancer at final pathology is about 30%, a result of undersampling by core biopsy.[39]

Breast cancer at extremes of age
Women 40 years old or younger with breast cancer require special consideration for treatment, and early review by a multidisciplinary team is recommended. Surgical management options (BCS or mastectomy) are the same as for women older than 40, but additional concerns in this age group include fertility preservation and contraception, pregnancy and breastfeeding after treatment, increased underlying genetic risk, breast reconstruction, sexual health, and psychosocial issues common to young families and working-age women.[40] Many centres across British Columbia are enrolling young women in a national study called RUBY (Reducing the bUrden of Breast cancer in Young women). This will provide a better understanding of the specific needs of these women and their oncologic outcomes.[41]

Older women may require a modified treatment plan as well. Women older than 70 years can have comorbidities that increase the risk posed by surgery and adjuvant treatments. Study results suggest that oncologic outcomes for this patient population may not be significantly affected by axillary staging[42] or adjuvant radiotherapy after BCS.[22] Alteration of the usual treatment course is only considered in older women with favorable tumor biology (e.g., estrogen-receptor-positive low-grade tumors), and multidisciplinary discussion is recommended to optimize outcomes while limiting morbidity related to treatment.

Neoadjuvant therapy 
Surgeons are often the first clinical specialist to discuss the diagnosis of breast cancer with a patient. The surgeon must then refer the patient to a medical oncologist in cases where it may be appropriate to begin by treating the patient systemically with neoadjuvant therapy. Patients with inoperable locally advanced breast cancer (LABC) or inflammatory breast cancer must start medical treatment prior to surgery. Currently, more patients with early, operable breast cancer (up to 15% of breast cancers) are being treated with NAT. If the patient is known to require systemic therapy regardless of findings from surgery and if their tumor is likely to respond favorably to systemic treatment (e.g., HER2-positive breast cancer), NAT can be considered. NAT can make it possible to use surgical techniques such as breast conserving surgery or skin sparing mastectomy that would be contraindicated otherwise, can allow time to complete genetic testing before making recommendations regarding the extent of surgery (e.g., to determine if a BRCA mutation makes a bilateral mastectomy appropriate), and can provide in vivo assessment of treatment response and prognostication associated with pathologic complete response (e.g., to determine if viable tumor cells are evident after systemic therapy).[14,15,43,44] Early multidisciplinary discussion for these patients is recommended.

Multidisciplinary discussion
Many clinical scenarios require multidisciplinary discussion. The multidisciplinary cancer conference (MCC) is designed to assist in clinical decision making and patient management by involving radiologists, medical and radiation oncologists, pathologists, and surgeons.[45] MCC review has been shown to provide care that adheres to known guidelines and alters management and treatment recommendations in 41% of cases,[46,47] but it is unclear from the literature if MCC improves clinical outcomes. Each community may have different ways to ensure multidisciplinary input for breast cancer cases and to determine which patients may benefit the most from MCC. Weekly multidisciplinary cancer conferences are routine at each of the six BC Cancer centres. Referral to BC Cancer for preoperative assessment is welcome, particularly when patients may benefit from neoadjuvant therapy or require a discussion of adjuvant therapy to aid in their initial surgical decision making. These appointments may facilitate discussion at the weekly conference, but in some circumstances patients not yet referred to BC Cancer may be discussed at these conferences after direct communication with a BC Cancer oncologist.

Summary
Surgical management of breast cancer has progressed significantly and is, in many cases, becoming more complex. Complexity arises from the multidisciplinary requirements of breast cancer patients, the need to balance cancer outcomes with morbidity related to treatment, evolving indications for radiotherapy and systemic therapy, and the quickly changing literature that supports different, and often less-aggressive, surgical techniques. General surgeons and surgical oncologists must be familiar with the wide spectrum of treatment options to allow for the best surgical management of their breast cancer patients. Participation in multidisciplinary cancer conferences, where available, or preoperative discussion of patients with local medical and radiation oncologists will help ensure that patients throughout BC receive optimal care. 

Competing interests
None declared.

Acknowledgments 
The authors wish to acknowledge the generous support of the BC Cancer Surgical Oncology Network, which permitted a series of meetings with surgeon representatives from all regional health authorities.


This article has been peer reviewed.


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Drs Warburton, Chiu, Wijayanayagam, Cader, Baliski, Sutter, Cheifetz, and McKevitt are surgeons in BC associated with the BC Cancer Surgical Oncology Network. Dr Roberts is a surgeon in Ottawa associated with the BC Cancer Surgical Oncology Network. As well, Drs Warburton, Chiu, and Cader are clinical instructors in the Department of Surgery at UBC; Drs Baliski and Sutter are clinical assistant professors; Dr Cheifetz is an associate professor; and Dr McKevitt is a clinical associate professor. Dr Wai is a radiation oncologist at the BC Cancer Vancouver Island Centre and a clinical associate professor in the Department of Surgery at UBC.

Rebecca Warburton, MD, FRCSC, Connie G. Chiu, MD, FRCSC, Amanda Roberts, MD, MPH, FRCSC, Akushla Wijayanayagam, MD, FRCSC, Sonia Cader, MD, FRCSC, Christopher Baliski, MD, FRCSC, F. Michelle Sutter, MD, FRCSC, Elaine Wai, MD, MSc, FRCPC, Rona E. Cheifetz, MD, MEd, FRCSC, FACS, Elaine McKevitt, MD, MEd, FRCSC, FACS. Current surgical management of breast cancer . BCMJ, Vol. 60, No. 2, March, 2018, Page(s) 92-98 - Clinical Articles.



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