Keywords brentuximab vedotin - breast implant-associated anaplastic large cell lymphoma - breast
implant - neoadjuvant therapy - capsulectomy
Introduction
Anaplastic large cell lymphomas (ALCLs) are a group of mature CD30+ T-cell lymphomas
characterized by the proliferation of large and pleomorphic cells with similar immunophenotypic
features but a variety of clinical characteristics.[1 ] ALCLs are divided into four distinct subtypes: anaplastic lymphoma kinase (ALK)-positive,
ALK-negative, primary cutaneous, and breast implant-associated (BIA-ALCL).[1 ] BIA-ALCL is an uncommon CD30+ and ALK lymphoma typically occurring in women 8 to
10 years following breast implantation for breast augmentation or reconstruction.[2 ] In 1997, Keech and Creech reported the first case of ALCL in proximity to a textured
saline-filled breast implant 6 years following bilateral breast augmentation.[3 ] As of January 2011, the U.S. Food and Drug Administration (FDA) declared a possible
correlation between breast implants and ALCL, and in May 2016, the World Health Organization
(WHO) recognized BIA-ALCL first as a provisional, and then in 2022 as a definitive
T-cell lymphoma entity.[1 ] The current lifetime risk of BIA-ALCL, according to the American Society of Plastic
Surgeons (ASPS), is estimated to be 1:2,207 to 1:86,029 for patients with textured
implants.[4 ] Although the molecular pathogenesis is poorly established, numerous hypotheses have
been suggested including genetic predisposition, subclinical bacterial infection,
and a chronic inflammatory response following long-term immune stimulation to breast
implants.[5 ] The most common clinical presentation is a late onset of a periprosthetic effusion
and may be associated with breast distortion, swelling, and asymmetry. Less common
presentations may be a palpable mass, severe capsular contracture, lymphadenopathy,
or cutaneous erythema.[6 ] Due to the complex nature of this disease, a multidisciplinary approach involving
medical oncologists, hematopathologists, surgical oncologists, and plastic surgeons
is recommended for the management of patients with BIA-ALCL, particularly in case
of advanced disease or inoperable patients, with the aim of providing the best diagnostic
work-up, treatment, and surveillance strategies. The current National Comprehensive
Cancer Network (NCCN) consensus guidelines indicate bilateral breast implant removal
with en bloc surgical resection of the surrounding capsule in patients with disease
limited to the capsule.[7 ] According to FDA regulations, the prophylactic explantation of textured implants
is not recommended in asymptomatic BIA-ALCL patients; nevertheless, patients may discuss
the benefits and drawbacks of implant removal with their health care providers to
make an informed decision about their health.[8 ]
[9 ]
The use of adjuvant chemotherapy or radiation therapy is considered for patients with
local residual disease, positive margins, or surgically unresectable disease. Systemic
therapies include brentuximab vedotin (BV), an anti-CD30 monoclonal antibody, anthracycline-based
chemotherapeutic regimen CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone)
or CHOEP (cyclophosphamide, adriamycin, vincristine, etoposide, and prednisone), or
a combination of both are reserved for cases of residual or disseminated disease (stage
II–IV). There may, however, be a role for neoadjuvant therapy in advanced cases of
BIA-ALCL. Italian Ministry of Health guidelines on the diagnosis and treatment of
BIA-ALCL, recently published in November 2022, indicate the use of systemic chemotherapy,
BV, or a combination of both in the neoadjuvant setting in cases of stage IV disease.[10 ] Until now, few cases in the literature have reported the use of neoadjuvant therapy
for the treatment of locally advanced or disseminated diseases. We present two clinical
cases reporting the successful use of neoadjuvant therapeutic protocols in locally
advanced BIA-ALCL. The first case reports a 52-year-old patient with a left breast
mass-like stage III disease who underwent combined targeted immunotherapy and chemotherapy
(BV-cyclophosphamide, doxorubicin, prednisone [CHP]). Following a complete radiological
and metabolic response, the patient underwent bilateral implant removal, right total
intact capsulectomy, left en bloc capsulectomy, and skin resection from the left inframammary
fold in continuity with the capsule. The second case reports a 65-year-old patient
with right breast swelling and mass-like stage IIA disease who received targeted immunotherapy
with BV. Following a complete metabolic response and a significant reduction in mass
size, she underwent bilateral implant removal and en bloc capsulectomy. Both patients
provided written informed consent for the publication and use of their images.
Case
Case 1
A 52-year-old woman underwent bilateral subglandular breast augmentation in 1998 with
macrotextured silicone breast implants (Silimed 220 mL). She did not undergo breast
implant replacement since primary implantation. Physical examination showed bilateral
inframammary fold scars consistent with her previous breast surgery. The left breast
was slightly larger than the contralateral and a palpable breast mass in the lower-outer
quadrant was felt fixed to the implant capsule. Previous surgical procedures included
rhinoseptoplasty in 1989 and the removal of a fibroadenoma of the left breast in 2006.
Her past medical history included multiple thyroid nodules, sideropenic anemia, and
hiatal hernia. Daily pharmacological therapy included pantoprazole, levothyroxine,
sulfamethoxazole, and trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis during the 4 months of chemotherapy administration. Our patient
developed left breast heaviness and mastalgia as of December 2021. Breast and axillary
cavity ultrasound as well as 3D mammography failed to document pathological findings.
By February 2022, the patient noticed a palpable breast mass in the lower-outer quadrant
of the left breast followed by cutaneous erythema of the lateral aspect of the left
inframammary fold in March 2022 ([Fig. 1 ]). She underwent a breast MRI which did not show significant pathological findings.
By June 2022, after the failure of clinical improvement following an antibiotic and
anti-inflammatory treatment, a second breast MRI noted multiple radial breast implant
folds bilaterally and an area of altered mass-type enhancement approximately 5.0 cm × 4.0 cm × 4.2 cm
located in the lower-outer quadrant of the left breast and appeared fixed to the lateral
aspect of the left breast implant ([Fig. 2 ]). No focal or diffuse areas with altered enhancement were noted in the right breast
parenchyma. Multiple abnormal lymph nodes were observed in the left axilla, the largest
of which measured 1.8 cm × 1.2 cm, while no lymph nodal abnormalities were present
in the right axilla. Ultrasound-guided Tru-cut needle biopsy of the left periprosthetic
mass documented morphologic and immunohistochemical features (CD30 + , ALK-, CD3-,
CD5-, PAX5-, LMP1, cytokeratin AE1/AE3-, S100-) compatible with a BIA-ALCL ([Fig. 3 ]). Core biopsy from the left axillary lymph node documented fragments of a lymph
node structure with rare CD30+ large cells suspicious but not conclusive for lymph
node involvement of BIA-ALCL. One week later, a whole body PET-CT scan documented
a 5 × 4 × 2 cm metabolically active mass on the posterolateral aspect of the left
breast, multiple active lymph nodes in the ipsilateral axilla, left internal mammary
lymph node chain and left subpectoral lymph nodes (stage III, T4N2M0). Given the extent
of surgery necessary to achieve complete excision of pathological tissue, neoadjuvant
chemotherapy combined with targeted therapy was administered. From July to October
2022, she underwent a total of six cycles of neoadjuvant chemotherapy (doxorubicin,
cyclophosphamide, and prednisone) of which the second, third, and fourth cycles were
combined with BV. Immunotherapy was interrupted following the fourth cycle due to
peripheral neuropathy. Following the completion of four cycles of chemotherapy in
September 2022, the total body CT scan no longer documented pathological enhancement
of the left breast periprosthetic mass as well as a significant reduction in size
of the pathological axillary, subpectoral, and internal mammary chain lymph nodes.
After completion of six cycles of neoadjuvant chemotherapy, total body PET-CT scan
in November 2022 showed a complete metabolic response, and on December 1, 2022, breast
MRI demonstrated a total T response and a partial N response ([Fig. 4 ]). On December 12, 2022, the patient underwent bilateral implant removal, right total
intact capsulectomy, left en bloc capsulectomy with a 6 cm × 0.7 cm cutaneous resection
from the left inframammary fold corresponding to the site of the previous erythema
([Fig. 5 ]). Initial biopsy of axillary lymph node showed suspicious features, but not conclusive
for lymph node involvement. Given the excellent response to neoadjuvant therapy (complete
metabolic response on PET-CT), it was deemed acceptable to avoid the surgery to the
axilla and the risk of lymphedema. Close follow-up and interval ultrasound scans were
offered, and alternative options were discussed with the patient. Pathological examination
and immunohistochemistry of the breast capsule and skin resection showed no signs
of residual disease ([Fig. 6 ]). In view of an excellent preoperative radiological response and absence of residual
disease in the surgical specimen, no adjuvant radiotherapy or targeted therapy was
recommended. Thus far, she has had a complete response and an unremarkable postoperative
recovery without complications ([Fig. 7 ]). The patient has shown no evidence of disease reoccurrence after 12 months following
surgery.
Fig. 1 Preoperative clinical photographs in a 50-year-old patient with BIA-ALCL of the left
breast (A ). Our patient in June 2022 prior to neoadjuvant therapies and surgical treatment.
(B ) A close-up view of the cutaneous erythema of the lateral portion of the left inframammary
fold. BIA-ALCL, breast implant-associated anaplastic large cell lymphoma.
Fig. 2 Axial images from a breast MRI. (A ) Contrast-enhanced T1-weighted image shows a mass-like enhancement located on the
lateral aspect of the left breast implant. (B ) Contrast-enhanced T2-weighted image shows the same mass-like enhancement.
Fig. 3 Histology of the needle biopsy of the pericapsular mass showing aggregates of large
atypical CD30+ cells. (A–C ) Haematoxylin and eosin, original magnification (o.m.) ×400, ×300, and ×72. (D, E ) Immunostaining for CD30, o.m. ×350 and ×1,000.
Fig. 4 PET-CT scan images taken before and after neoadjuvant chemotherapy and targeted therapy.
(A ) Total body PET-CT scan taken in June 2022 showed a metabolically active mass on
the posterolateral aspect of the left breast. (B ) Total body PET-CT scan taken in November 2022 showed a complete metabolic response.
Fig. 5 The patient underwent surgery to have both breast implants and capsules removed.
(A ) Right total intact capsulectomy. (B ) Left en bloc capsulectomy together with skin resection from the left inframammary
fold in continuity with the capsule.
Fig. 6 Pathological examination of the left breast capsule.
Fig. 7 Clinical photograph taken 3 months following surgery.
Case 2
A 65-year-old woman presented with progressive right breast swelling and palpable
mass in the upper-inner quadrant ([Fig. 8 ]). Nine years earlier, she underwent bilateral mastopexy augmentation with silicone
macrotextured implants but denied previous breast problems. She had a history of chronic
obstructive pulmonary disease, rosacea, and pulmonary tuberculosis in childhood. She
underwent a hysterectomy and two cesarean sections. Her regular medications included
formoterol and salbutamol inhalers and lymecycline. She was a long-term smoker and
had a family history of cervical cancer, but no history of breast cancer or lymphoproliferative
disease. Her physical examination revealed inverted T-incisions (Wise pattern) and
a swollen right breast with a palpable 5 cm mass in the parasternal area, which was
firm and fixed to the sternocostal junction and third rib. A breast ultrasound confirmed
a large seroma, which was aspirated, and cytological features were suspicious, but
inconclusive for BIA-ALCL. Subsequent MRI and CT revealed a 5 × 4 × 3 cm mass infiltrating
the underlying pectoralis muscle. The diagnosis of BIA-ALCL was confirmed on core
biopsy from the chest wall mass, which showed large, atypical cells with strong expression
of CD30, some staining with epithelial membrane antigen and CD45, but negative for
CD5, CD20, CD79a, and epithelial markers. Further immunochemistry tests were positive
for CD4, but negative for ALK1, PAX5, CD2, CD7, and CD8. A PET-CT confirmed FDG-avid
(SUV max 7.2) mass infiltrating beyond the implant capsule (stage IIA, T4N0M0). The
anticipated extent of surgical procedure at this stage involved excision of the mass
en bloc with capsulectomy and partial resection of ribs and sternum. In view of the
significant morbidity and high risk of surgery, neoadjuvant therapy with BV was recommended
to downstage the disease and ensure radical excision. The interval PET-CT after the
first four cycles of BV showed a Deauville 1 metabolic response with residual mass,
therefore further four cycles of BV were administered. Subsequent PET-CT confirmed
a complete metabolic response and a significant reduction in the size of the mass.
A surgical procedure was performed at this point, involving bilateral en bloc capsulectomy
and implant removal (Allergan CUI 410 mL). Small peri-implant seroma was also aspirated
intraoperatively. At surgery, there was no evidence of pectoralis muscle infiltration
with a clear dissection plane around the capsule, however, multiple muscle biopsies
were performed for histology. The surgical specimen, chest wall biopsies, and immunochemistry
tests of the seroma did not reveal any residual disease. In view of the complete pathological
response, no further immunotherapy or radiotherapy was recommended. The patient made
uneventful postoperative recovery; however, she had myocardial infarction 2 months
after surgery, which required coronary stenting and anticoagulation ([Fig. 9 ]). The PET-CT performed 8 months after surgery confirmed complete metabolic remission
as previously reported.[11 ] She is now 4 years postsurgery and remains well with no evidence of recurrence ([Fig. 10 ]).
Fig. 8 Clinical photographs at presentation. Visible breast asymmetry, large seroma, and
palpable mass in the right upper-inner quadrant.
Fig. 9 Clinical photograph on the 19th postoperative day (previously included in an early
report).
Fig. 10 (A ) PET-CT at presentation demonstrating large peri-implant seroma and metabolically
active parasternal mass infiltrating pectoralis muscle and closely attached to rib
and sternum. (B ) PET-CT after 4 cycles of BV. (C ) PET-CT after 8 cycles of BV. BV, brentuximab vedotin.
Discussion
BIA-ALCL is an uncommon and emerging form of peripheral T-cell lymphoma diagnosed
in patients with a history of textured breast implants. The etiology of this condition
is still poorly understood, however current evidence indicates possible transformation
and clonal expansion of deregulated immune cells as a response to chronic exposure
to inflammatory cytokines in a genetically susceptible individual.[8 ]
[12 ] The majority of patients present at early stages of the disease with peri-implant
effusion and breast swelling. In the systematic review by Leberfinger et al, 66% of
patients were seen initially with seroma, 8% with a mass, 7% with mass and seroma,
and 18% with other symptoms such as capsular contracture, axillary lymphadenopathy,
and skin lesions.[13 ] One of our cases presented with skin rush, mass, and lymphadenopathy whereas the
other with mass and seroma. Surgical resection remains the standard of care for patients
with BIA-ALCL and includes explantation, total intact capsulectomy, and en bloc resection
of all associated masses and involved lymph nodes. The technical aspects of this procedure
were described by Tevis et al,[14 ] who recommended en bloc resection of breast implants with surrounding capsules,
utilizing existing scars. Some patients may require skin excision in case of local
involvement or close proximity of the mass, which may be incorporated in planned Wise-pattern
mastopexy to reduce redundant skin after explantation but may occasionally require
a separate incision. Tumescence of the posterior part of the capsule during total
capsulectomy can be useful in the case of subpectoral implants, where the capsule
is usually densely adherent to the periosteum and ribs, and inadvertent injury can
lead to pneumothorax.[14 ]
[15 ] Every effort should be made to remove the entire capsule and avoid spillage of malignant
effusion into the cavity. To mitigate this risk, an ultrasound-guided aspiration of
the seroma just before surgery may be considered. The oncological radicality of surgery
is essential for successful long-term outcomes as evidenced in several publications.[8 ]
[15 ]
[16 ] Clemens et al reported improved overall survival (OS; p < 0.001) and event-free survival (EFS) in patients treated with complete surgical
excision compared with other therapeutic interventions. Only 5% of patients treated
with complete excision had further events, which underlines the importance of achieving
clear margins, regardless of adjuvant therapy regimens. However, the stage of BIA-ALCL
at diagnosis had a significant effect on EFS. The rate of events was 2.6-fold higher
for stage II and 2.7-fold higher for stage III disease compared with stage I disease
in this case series.[17 ] Moreover, the size of the tumor and local invasion adversely affect the prognosis,
as indicated by the event rate of 14.3% for stage T4 compared with 0% for stages T1/T2,
even if complete resection was achieved.[8 ]
[17 ] In a recent systematic review including 178 BIA-ALCL cases, Naga et al found that
presentation with mass as opposed to a seroma was significantly associated with recurrence
and mortality (odds ratio of 19.4).[18 ] Management of locally advanced or surgically unresectable BIA-ALCL poses a significant
challenge and requires a multidisciplinary approach. Early experience with the use
of systemic chemotherapy and regimens including cyclophosphamide, doxorubicin, vincristine,
and prednisolone, showed variable response. In a study of 87 BIA-ALCL cases published
by Clemens et al,[17 ] over 50% of patients received chemotherapy and approximately one-third of these
patients experienced progression of the disease or did not achieve a response. Eleven
patients were treated with systemic chemotherapy and never underwent complete surgical
excision, and six of these patients died as a result of the disease. The authors concluded
that systemic chemotherapy alone was insufficient to control the disease. A retrospective
review of 39 patients with locally advanced BIA-ALCL (stage IIB–IV) by Collins et
al[19 ] showed much lower rates of definitive surgery (59%), higher mortality (20.8%), and
lower rates of complete remission (71.8%) in this group compared with early-stage
BIA-ALCL. Very rapid disease progression (hyperprogression) was observed in five patients
(12.8%) who had only limited surgery, indicating a possible detrimental effect of
incomplete BIA-ALCL excision.[18 ] Poor outcomes of locally advanced BIA-ALCL prompted interest in neoadjuvant systemic
therapies to downstage the disease and enable complete surgical excision. Recently
published NCCN guidelines[7 ] recommend adjuvant chemotherapy in advanced BIA-ALCL (stage II–IV) with either CHOP,
CHOEP, or CHP + BV regimens. The efficacy of immunochemotherapy in the treatment of
CD30+ peripheral T-cell lymphomas was also demonstrated in the ECHELON II trial, which
exhibited statistically superior progression-free survival and OS compared with standard
anthracycline-based chemotherapy.[19 ]
[20 ] Single-agent immunotherapy with BV as CD30 targeting antibody–drug conjugate is
also an interesting therapeutic option, particularly for nonresponders to standard
chemotherapy.[21 ]
[22 ] BV is an antibody–drug conjugate composed of an anti-CD30 chimeric antibody conjugated
to monomethyl auristatin E, the microtubule-disrupting agent. The primary mechanism
of action is targeted delivery of monomethyl auristatin E to CD30-expressing tumor
cells. Additional proposed mechanisms that may contribute to the clinical activity
of BV include antibody-dependent cellular phagocytosis and immunogenic cell death.
However, the data on the treatment of BIA-ALCL in neoadjuvant settings are limited
and based mainly on case reports ([Table 1 ]).[11 ]
[16 ]
[23 ]
[24 ]
[25 ] Therapeutic decisions are extrapolated from experience with systemic and refractory
ALCL, due to a lack of prospective studies and rarity of BIA-ALCL. Coombs et al reported
on two cases of locally advanced BIA-ALCL (stage III) treated with neoadjuvant therapy
(CHOEP and BV) with excellent clinical and pathological response. Both patients presented
with large tumors and underwent extensive surgical procedures, including chest wall
reconstructions, due to hypermetabolic activity on interval PET-CT and concerns about
possible residual disease, however, final results confirmed a complete pathological
response.[16 ] Stack and Levy[22 ] described the complete clinical and radiological response to monotherapy with BV
in a case of unresectable ALCL. The patient received also palliative radiation therapy
and remained in remission at 20 months after therapy. A combination of BV and vincristine
was successfully used in neoadjuvant settings by Caputo et al[24 ] in the case of massive, fungating mass-like BIA-ALCL, infiltrating pectoralis muscle
(stage IIA). The patient underwent radical excision followed by adjuvant BV and COMP
chemotherapy and remained in complete remission for 12 months. Excellent response
to neoadjuvant chemotherapy (CHOEP) in stage IV BIA-ALCL was also reported by Thibodeau
et al.[23 ] Despite significant complications (pulmonary embolism and pancytopenia), the patient
completed five cycles of CHOEP with complete resolution of hypermetabolic areas on
PET-CT and no residual disease in the surgical specimen. All the above case reports
are consistent with our experience with neoadjuvant therapy in two cases of advanced
BIA-ALCL.
Table 1
Literature review on neoadjuvant therapy in locally advanced breast implant-associated
anaplastic large cell lymphoma
Author
Year
Stage
Neoadjuvant therapy
Surgery
Pathological response
Adjuvant therapy
Outcome
Thibodeau et al[23 ]
2019
IV
CHOEP
5 cycles
Bilateral explantation + en bloc capsulectomies. Wire-guided excision of left axillary
and lateral breast masses
Complete
No
Complete remission at 8 months posttherapy
Allchin et al[11 ]
2020
IIA
BV
8 cycles
Bilateral explantation + right en bloc capsulectomy + chest wall biopsies
Complete
No
Complete remission at 18 months postsurgery
Caputo et al[24 ]
2021
IIA
BV + Vincristine
Excision of fungating, necrotic tumor en bloc with implant and pectoralis muscle.
Dermal substitute for coverage and subsequent skin grafting
Partial/Complete excision + skin grafting
Yes: BV + COMP
5 cycles
Complete remission for 12 months/Died of cardiovascular disease
Coombs et al[16 ]
2021
III
CHOEP
4 cycles
Initial open biopsy for diagnosis. Definitive procedure after neoadjuvant therapy—left
anterior capsulectomy, partial breast excision, anterior chest wall resection (including
third to fifth ribs) + reconstruction with Prolene mesh and methacrylate
Complete
No
Complete remission at 4 years postsurgery
III
BV
8 cycles
Incisional biopsy of right chest wall mass. Definitive surgery after completion of
neoadjuvant immunotherapy—chest wall mass resection (including third to fifth ribs) + reconstruction
with pedicled latissimus dorsi flap + Prolene mesh and methacrylate. Postoperative
hematoma and pleural effusion requiring drainage
Complete
No
Complete remission at 3 years postsurgery
Premji et al[25 ]
2022
III
CHP + BV
6 cycles
Resection of right chest wall tumor (including third to fifth ribs), partial sternectomy,
thymectomy, en bloc removal of the implant + reconstruction with mesh/bone cement
and serratus advancement flap. Postoperative chest wall incision necrosis requiring
debridement, washout, and tissue transfer
Partial/Complete excision + chest wall reconstruction
Yes:
Radiotherapy
Auto-SCT
BV (12 cycles)
Complete remission at 1-year post auto-SCT
Abbreviations: Auto-SCT, autologous stem cells transplant; BV, brentuximab vedotin;
CHOEP, cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone; CHP, cyclophosphamide,
doxorubicin, prednisone; COMP, cyclophosphamide, liposomal doxorubicin, vincristine,
prednisone, rituximab.
The limited sample size of this study and the paucity of literature regarding neoadjuvant
therapeutic regimens underline the need for larger-scale studies to validate current
findings. Although the results of the present case report as well as those reported
in the literature are promising, surgical management remains the standard care of
locally advanced BIA-ALCL and should always be performed in accordance with the most
recent guidelines in the best interest of the patient. Similar to the patients reported
in this study, suitable candidates for neoadjuvant therapeutic regimens include locally
advanced cases of BIA-ALCL with surgically unresectable disease due to extension in
the chest wall, patients with lymph node involvement, and those suitable to undergo
chemoimmunotherapy or immunotherapy alone. The potential benefits of administering
neoadjuvant therapeutic regimens may promote surgical de-escalation, in terms of a
reduction in the extent of surgical intervention and change its timing. It is, however,
important to underline that neoadjuvant therapies do not indicate avoidance surgery
and must be performed in accordance with current guidelines. Therefore, tumor downstaging
signifies a reduction in surgical extent as well as potential side effects associated
with surgery.
To assess the long-term outcomes of immunotherapy in locally advanced BIA-ALCL, the
patients should be closely monitored according to NCCN guidelines: clinical and radiological
follow-up every 3 to 6 months for the first 2 years and subsequently annual review
until 5 years posttherapy. The interval PET-CT provided important information about
response and determined the duration of treatment and timing of surgical intervention.
Complete surgical excision and complete pathological response were achieved in both
patients after PET-CT confirmed the resolution of metabolically active disease. Both
patients received BV, which proved to be very effective as single-agent or combined
therapy. Several authors reported that BV is a potential alternative to cytotoxic
chemotherapy and is characterized by excellent response rates and a favorable tolerability
profile.[16 ]
[22 ]
[24 ]
Conclusion
The optimal management of patients with advanced BIA-ALCL and possible chest wall
invasion remains unclear. Although surgery is an essential part of treatment, the
extent and timing of surgical intervention should be carefully planned and warrant
multidisciplinary discussion, especially when primary, radical resection is uncertain.
We believe that in such cases, neoadjuvant therapy should be strongly considered.
Monitoring of the response to neoadjuvant therapy is essential and may necessitate
modification of the treatment plan.
Our experience supports the concept of neoadjuvant therapy in the management of locally
advanced BIA-ALCL, which can offer downstaging of the disease, de-escalation of surgery,
and reduce the risk of significant complications. Based on emerging evidence, targeted
immunotherapy with BV as monotherapy or in combination with chemotherapy, seems to
be a preferred induction therapy in such cases, offering good response rates and an
acceptable tolerance profile. Further genomic research and clinical data from larger,
controlled studies may provide further evidence on patient selection and optimal management
of locally advanced BIA-ALCL.
