Advances in Oncoplastic Breast Surgery

Louis Chow Wing-Cheong

【Abstract】 Evidence from six prospective,randomized trials has shown that breast-conserving surgery （BCS） is a safe alternative to mastectomy,and this led to a heightened interest in achieving and balancing local control and cosmetic outcome post-surgery.However,it is also becoming apparent that conventional BCS techniques may not produce cosmetically favorable results for patients who present with ill-defined or poorly situated breast tumors.Other factors that are commonly found in Chinese women,such as small-volume and denser breasts,also contribute to the difficulty in achieving an optimal cosmetic outcome post-surgery,thus necessitating the need for oncoplastic breast surgery techniques to be employed.This article serves as an overview of the recent advances and principles of oncoplastic breast surgery,as well as the use of autologous fat grafts to improve cosmetic results and eliminate remaining smaller deformities post-surgery.

【Key words】Oncoplastic;Breast cancer;Breast-conserving surgery;Fat graft

Breast-conserving surgery（BCS） and factors affecting prognosis

In 1894,an important milestone was achieved in breast cancer’s surgical treatment with the advent of the radical mastectomy by William Halsted［1］.The operation includes removing the entire breast,chest wall muscles,and axillary lymph nodes,which was modified in 1967 after extending Halsted’s radical mastectomy was proven to produce little benefit compared with the modified radical mastectomy which spares the muscles.A minimally invasive procedure then continues to gain traction,with the BCS or lumpectomy being performed in 1981.In stark contrast to Halsted’s era,the BCS only includes removing the primary tumor,the margin of surrounding normal breast tissue,and sentinel lymph nodes（if needed）.

The survival of patients who had undergone lumpectomy and radiotherapy was equivalent to those who had undergone a mastectomy,based on evidence from six prospective,randomized trials［2］.Minimizing local recurrence is clinically important,and the optimal surgical margin width remains vital to be discussed.However,the likelihood of local recurrence following BCS is also related to the underlying tumor biology and the availability of effective adjuvant therapy such as tamoxifen for estrogen receptor-positive tumors.

A positive surgical margin at the edge of the tissue,together with tumor size larger than 2 cm,positive lymph nodes,and young age,are known to be predictive factors of ipsilateral breast tumor recurrence （IBTR）［3］.Margin distances taken from all directions（i.e.,superior,anterior,inferior,posterior/deep margins）can be determined by gross measurement and microscopic measurement.However,the latter is usually more accurate,especially for close margins.An optimal and achievable margin width may vary on a case-to-case basis.For example,some cases could present with an anterior margin at 5 mm,but others could present with a much closer anterior margin at 2 mm.Revesz［4］has summarized the findings of randomized trials of breast conservation.A negative margin originally proposed by the National Surgical Adjuvant Breast and Bowel Project（NSABP）was the absence of tumor cells at the ink.After a follow-up period of 20 years,14.2% experienced IBTR.Other large studies using grossly free margins,such as those conducted by the European Organisation for Research and Treatment of Cancer（EORTC）and the National Cancer Institute（NCI）,found a 13-year IBTR rate of 19.7% and a 10-year IBTR rate of 18%,respectively.In terms of determining the safety of a narrow margin at≤2 mm,the findings remain controversial with two of the newer studies reporting conflicting results［5-6］.

Tumor location is also an important factor that impacts prognosis.A Surveillance,Epidemiology,and End Results（SEER）population-based study that analyzed data from more than 300,000 women with breast cancer found that breast cancer-specific mortality was affected by the primary tumor site［7］.Survival curves showed that breast cancerspecific survival was the highest with primary tumor cases in the upper-outer quadrant（UOQ）.Other studies also suggested that the risk of dying increased significantly when the tumor is further located from the axilla［8-9］.An excess risk of relapse and mortality was associated with tumors located in the inner or medial region of the breasts,and similar findings have been found in the Chinese population［10］.

The challenge of performing BCS in Chinese women

Meanwhile,the disease burden of breast cancer continues to increase over the past few decades.The annual percent change in the mortality rate of women with breast cancer in China was 0.4（95%CI,-0.7 to 1.5）between the years 1987 and 1995,but it rose to 4.1（95%CI,2.1 to 6.2）between the years 1995 and 2000［11］.According to the 2015 Chinese Cancer Statistics,breast cancer incidence and mortality rate continued to show an upward trend between the years 2000 and 2011［12］.Early detection and access to optimal treatment are necessary to reduce the incidence and mortality rates of breast cancer,but there are some key obstacles which are particularly relevant in the Chinese population.

Other than the problems of cost and access to diagnosis and treatment in certain rural areas and lack of acceptance for breast cancer screening,Chinese women with breast cancer tend to be diagnosed at a younger age than their western counterparts.According to the China Anti-Cancer Association and National Clinical Research Center for Cancer［13］,the peak onset of age for breast cancer in Chinese women is between 40 and 50 years.A separate study by Zheng［14］reported that the proportion of premenopausal cases was as high as 62.9% in China,which is comparably much higher than the proportion reported in the western population.

An elevated mammographic density,an established risk factor for breast cancer,is also more prevalent in Chinese women.A national cancer screening program in 11 urban provinces in China that included 11,478 women found that heterogeneously dense breasts were the most common category for premenopausal and postmenopausal women［15］.Heterogeneously dense breasts（categorized as Breast Imaging-Reporting and Data System ［BI-RADS］3）were detected in 65% of premenopausal women and 41.6% of postmenopausal women,whereas extremely dense breasts（categorized as BI-RADS 4）were detected in 4.4% of premenopausal women and 1.9% of postmenopausal women.The proportion of women with dense breasts（either BI-RADS 3 or 4）was 25% in women aged between 65 and 69 years,but it reached 72.9% in women aged between 45 and 49 years.

Since Chinese women generally have small-volume breasts,denser breasts,and a younger peak onset of age for breast cancer［15-16］,these factors contribute to the challenge of achieving and balancing local control and cosmetic outcome in Chinese women who need to undergo breast surgery.In large breast tumors related to breast size,ill-defined,or poorly situated tumors,conventional BCS may not produce cosmetically favorable results［17］,thus necessitating the need for oncoplastic breast surgery techniques to be employed.

Oncoplastic surgery techniques and the use of autologous fat grafting（AFG）

Several oncoplastic techniques can be considered depending on the tumor size and breast size［18-22］,with a varying degree of cosmetic outcome post-surgery.Fundamentally,the oncoplastic surgery techniques for breast reconstruction include two different approaches.The first approach is known as volume displacement,which utilizes glandular reshaping or reduction techniques.Volume displacement techniques to consider for moderate-to large-breast size include reduction mammoplasty or mastopexy,omegaplasty（batwing mastopexy）,extended superior-lateral pedicle,extended inferior pole pedicle,and lateral pedicle with up-rotation of the whole breast.On the other hand,volume displacement techniques to consider for patients with smaller breast size are periareolar or round block techniques,modified round block technique,tennis racket method,and matrix rotation.

The second approach is known as volume replacement,in which autologous tissues are used to fill the defect postsurgery and replace the volume of the excised breast tissue.Yang［21］provided a comprehensive review of the volume replacement techniques that can be considered for patients with small-to moderate-sized breasts.The volume replacement techniques that can be considered include an adipofascial flap,a lateral thoracodorsal flap,a thoracoepigastric flap,an intercostal artery perforator flap,a thoracodorsal artery perforator flap,and a latissimus dorsi myocutaneous flap.

Additionally,AFG is a minimally invasive breast reconstruction technique that can improve cosmetic results and eliminate remaining smaller deformities post-surgery.This technique involves the harvesting of small amounts of patient’s fatty tissue via liposuction and grafting them into the area with deformity to improve breast shape and volume,thus correcting the symmetry of both breasts.Depending on the patient’s natural fat deposits,the fatty tissue can be harvested from the abdomen,inner thighs,buttocks,and lumbar region.In general,harvesting the fatty tissue from the abdominal area is preferable because this does not require changing the patient’s body position during the procedure and most patients would appreciate the loss of the abdominal fat.Areas such as the buttocks and lumbar region should be considered for harvesting when the fatty tissues from the abdomen and inner thighs are insufficient.

The oncologic safety of performing AFG in breast cancer patients

In contrast to other filling materials and silicone implants,the grafted fat is a viable tissue that can potentially influence the microenvironment of the transplant site and requires neovascularization to promote its survival［23］.This leads to concerns over the risk of locoregional recurrence because several in vitro and preclinical studies have suggested that adipose-derived stem cells（ADSCs）,which can be found in the grafted fat,may potentially influence residual tumor cells in the transplant site to reproduce due to the secreted growth factors［23-24］.Nevertheless,this hypothesis remains debatable and there are discrepancies between the clinical and experimental data.For instance,some may argue that the fat grafts used in experimental studies do not reflect those used in the clinical setting,especially when the experimental study was conducted in animals.

Since it is difficult to assign an acceptable and ethical alternative to AFG in prospective randomized controlled trials,the clinical evidence on AFG is mainly available as retrospective case series and matched cohort studies.Krastev［25］conducted a meta-analysis on a total of 59 studies that included 4,292 breast cancer patients who had undergone AFG.This meta-analysis did not find an increased risk of locoregional recurrence with AFG.The difference in the incidence rate of the matched cohort studies was 0.15（95%CI,0.36 to 0.07,P=0.419）,and this was confirmed in the pooled results that included the remaining cohort studies and case series.

One of the most recent evidence on the safety of AFG came from a matched cohort study by Stumpf［24］.This study included 65 patients who underwent BCS and simultaneous AFG,then matched them with 255 patients who underwent BCS alone.With a mean follow-up duration of 5 years,there was no significant difference in the annual locoregional recurrence rate（0.86% in those who received immediate AFG vs.0.7% in those who underwent BCS alone）.However,the study found that the number of involved axillary nodes was the sole independent risk factor for recurrence（P=0.045）.

These findings,therefore,suggest that AFG can be performed safely to achieve an optimal cosmetic outcome post-BCS.A careful and comprehensive assessment for the risk of recurrence should be performed in patients who want to receive AFG,and those with a high risk of recurrence should perhaps delay receiving AFG and undergo re-evaluation over time［26］.

Principles to achieve an optimal cosmetic outcome post-surgery

With the primary location of the tumors divided into UOQ,upper-inner quadrant （UIQ）,lower-outer quadrant（LOQ）,lower-inner quadrant（LIQ）,and nipple and central breast（central）,the study that analyzed the data of 1,044 Chinese women with breast cancer found that tumors located in the UOQ were the most common at 50.2%,followed by UIQ at 21.9%,LOQ at 11.9%,central at 10.3%,and LIQ at 5.7%［10］.Considering that tumor location,as well as breast size,the volume of lumpectomy resection,type of incision（circumareolar or skinexcision with lumpectomy）,post-operative complications,and planning and techniques of radiation therapy are important factors affecting breast cosmesis after surgery,oncoplastic breast surgery techniques should be employed to achieve and balance local control and cosmetic outcome.

Amongst the breast quadrants mentioned above,tumors located in the UIQ are considered challenging to remove without causing a certain degree of breast deformity or displacement of the nipple-areola complex（NAC）.In two representative cases,Lin［27］showed that it was difficult to perform a BCS with a tumor in the UIQ of medium-and large-sized breasts.UIQ has the least amount of glandular tissue,and without the proper surgical technique or by doing a wide excision in this location,the visible breast line can be distorted post-surgery and therefore affecting the overall quality of the breast shape.In performing BCS in the UIQ,factors such as breast ptosis,the volume of remaining breast tissue post-surgery,and wound placement and healing should be carefully assessed and planned.These factors should also be considered when performing BCS in other quadrants,especially when the tumor size is large relative to the size of the breast.

There are several principles that should be considered in an attempt to achieve an optimal cosmetic outcome postsurgery.The first principle is related to the skin incision.The incision for a traditional lumpectomy is placed directly over the tumor,but this would result in a scar that is visible when healed.In contrast,oncoplastic breast surgery techniques utilize a hidden scar lumpectomy, by performing an incision in a place that is hard to see and resulting in a hidden scar when healed.

Whenever possible,the oncoplastic breast surgery technique utilizes a circumareolar type of incision such as the round block technique is preferred due to the‘envelope effect’.This technique is especially suitable for patients with smaller breast size and periareolar lesions because the scar will be less visible,thus producing a good cosmetic outcome.For lesions located distant from the nipple,a modified form of the round block technique can be considered［22］.An easier access to these distally-located lesions would be available by subcutaneously dissecting all sides of the NAC.If the lesions are located further away and the round block technique is difficult to use,other techniques such as the tennis racket method can be considered.However,this technique requires an additional wedge-shaped incision line towards the direction of the lesion.Therefore the cosmetic outcome of the breast would be affected by a visible scar.

The second principle to achieve an optimal cosmetic outcome post-surgery is related to breast symmetry.There are many ways to achieve and maintain good breast shape and symmetry,and the degree of ptosis should be considered.The NAC is the primary landmark of the breast that plays an important part in achieving breast symmetry postsurgery.The repositioning of the NAC of the contralateral breast,together with volumetric adjustment,can be performed to improve the cosmetic appearance of the breasts post-surgery.

Thirdly,to reduce fibrosis and scarring,the blood supply of the breast tissue flap should be carefully designed.This should be planned and considered together with the fourth principle,in which breast radiation is also important,and the number of fractions may affect the consistency（texture）of the reconstructed breast.It is difficult to predict the degree of change in breast consistency after radiotherapy,but certain approaches can be planned preoperatively considering the effects of radiation.For example,Rose［28］found a predictable and reliable symmetry post-surgery by leaving the breast that will undergo radiation around 150-200 cm3larger than the other breast.Nonetheless,the effect of radiation on breast consistency remains important to be discussed with the patients to adjust their expectations.

Conclusions

Over the past few decades,the advances in oncoplastic breast surgery techniques have considerably improved the cosmetic outcome following breast surgery.Efforts at improving these techniques will continue to increase since it is clear that oncoplastic breast surgery techniques are here to stay.It is imperative that breast surgeons adopt the techniques according to their patients’needs and understand that an optimal cosmetic outcome post-surgery starts with careful and thorough planning prior to surgery.