This study emphasizes two important points: first, the high feasibility of BCS after neoadjuvant chemotherapy, and second, the good tolerability of patients to treatment with low incidence of grade 3 and grade 4 toxicity.
In the present study, after neoadjuvant chemotherapy, 36 out of 45 patients showed partial response with post chemotherapy tumour size ≤5 cm. This figure of response is within the range of the reported studies where Newman et al. [10
] found that 75% of patients were feasible to BCS. The overall objective response of the primary tumour in patients with locally advanced breast cancer ranged from 71% to 87% [11
]. On the other hand, our results are much higher than that reported by Yadav et al. [13
] who found that only 23% of patients with locally advanced breast cancer were candidates for BCS after neoadjuvant chemotherapy. This difference could be explained on the ground that the reported study used anthracycline based chemotherapy (FAC regimen) while in the current study we used taxene based chemotherapy (TAC regimen).
The vast majority of our patients (41 patients, 91%) had large tumour size (> 5 cm), 10 patients of them (22.2%) had T3N0 (stage IIB), 25 patients (55.6%) had T3N1 (stage IIIA) and only 6 patients (13.3%) had fixed nodes (stage IIIA). Our figures are different than those reported by Formenti et al. [14
] where 36% patients had stage IIB (T3N0) tumours, 30% had stage IIIA, and 34% had stage IIIB. This may be due to exclusion of stage IIIB cases in our study.
The mean prechemotherapy tumour size was 6.4 ± 1.4 cm in the present study which was similar to that reported by Chen et al. [15
] where the median tumour size before chemotherapy was 6.0 cm. Our figure is also comparable with that reported by Viswambharan et al. [12
] where the size of the primary tumour ranged from 5-9 cm (mean = 7.1 cm). The mean post-chemotherapy tumour size in our study, was 3.9 ± 1.3 cm which was comparable to figures reported by Chen et al. [15
] (2.2 to 3.2 cm) and Viswambharan et al. [12
] (3.8 cm).
In the current study, we found that stage, grade, and HR were not statistically significant on the response to chemotherapy. However, the reported series showed that nuclear grade[16
] and HR negative status[17
] were significantly related to tumour response to preoperative chemotherapy. This difference may be explained by the larger number of patients in the reported series (287 patients in Abu-Farsakh et al. [16
], 60 patients in Sarid et al. [17
], and 399 patients in Collini et al. [18
]). All patients with post chemotherapy tumour size <4 cm underwent BCS with negative surgical margins whereas only 46.2% of those (6 out of 13 patients) with post chemotherapy tumour size between 4 and 5 cm were feasible for BCS with negative margins. This is in agreement with Neuman et al. [10
] who stated that post-chemotherapy tumour size less than 4 cm is a favourable criterion regarding the feasibility of BCS.
The rate of positive margins, in our study, was 19.4% (7 out of 36 patients) which was higher than that observed by Mittra et al. [19
] where only 2.4% of patients with BCS showed positive margins. This difference may be explained by the larger number of patients in their study (726 patients) than in our study (36 patients).
All patients with post chemotherapy tumour size <4 cm underwent BCS with negative surgical margins whereas only 46.2% of those (6 out of 13 patients) with post chemotherapy tumour size between 4 and 5 cm showed negative margins. After re-resection most of patients with positive margins (5 out of 7 patients; 71.4%) achieved negative margins, but with compromised cosmetic appearance. This can be explained on the ground that, there was a significant association between pre-chemotherapy tumour size and histopathological margin status. There was also, a significant association between post-chemotherapy tumour size and histopathological margin status[12
]. In patients with post-chemotherapy tumour size >4 cm, 10/13 (77%) were margin positive and 3/13 (23%) were margin negative whereas in patients with post-chemotherapy size >3 cm, 13/24 (54%) were margin positive and 11/24 (46%) were margin negative. In patients with post-chemotherapy size <3 cm, 1/6 (17%) were margin positive and 5/6 (83%) were margin negative. Therefore a smaller post-chemotherapy size is found to give lesser margin positivity and better cosmetic appearance. Therefore the recommendation for breast conservation surgery was for tumours up to 4 cm[20
In this study, the median follow up time from the date of registration in outpatient clinic was 24 months (range 21-30 months). The relapse rate among patients who underwent conservative surgery was 5.9% (2 out of 34 patients). This figure is identical to that reported by Mittra et al. [19
] who found a 5.9% relapse rate among patients in the conservative surgery group. Another study from the M. D. Anderson Cancer Centre evaluated outcome after induction chemotherapy and BCT for 93 patients with locally advanced or large primary breast cancers and found a local recurrence rate of <10%. This was comparable to the local recurrence rate seen in patients with early-stage breast cancer treated with a breast-conserving approach[21
It is reassuring to note that the tolerance to preoperative chemotherapy was very good. Adverse effects were mostly of grade 1 or 2 severities. Grade 4 leucopenia was observed in only 3 cases. The most common toxicity criteria following neoadjuvant chemotherapy among our patients was fatigue (88.9%). This is matched with Sarid et al. [17
] who found that adverse effects were mostly of grade 1 or 2 and the most common side effect was fatigue. Alopecia was observed in 84.4% of cases. This is comparable with Formenti et al. [14
] who observed a 92.7% rate of alopecia in their study (38 of 41 patients). Athralgia and myalgia developed in 17.8%, diarrhoea in 11.1% and mouth sore in 8.9%. Febrile neutropenia (who were admitted for treatment) occurred in only 6.7% of patients. Formenti et al. [14
] found similar results where arthralgia was observed in 17%, stomatitis in 12%, and febrile neutropenia in 9.7% of patients. On the other hand, Chen et al. [15
] found a lower incidence of febrile neutropenia (2%) which may be due to their use the regimen of weekly taxol which is more tolerable with fewer side effects.
It is interesting that no RT pneumonitis occurred among the patients accrued to this study. There was also no severe cardiac toxicity. The finding is consistent with the University of Washington's experience and is in contrast with that reported by Yu et al. [22
] who observed RT pneumonitis in 19% of 21 breast cancer patients treated by concurrent paclitaxel and RT and 20% of 16 patients who received RT after paclitaxel. Both groups of patients, however, were treated postoperatively and after doxorubicin-based chemotherapy. It is possible that the sequencing of anthracycline-based chemotherapy and taxanes affects the pulmonary morbidity of subsequent RT therapy[14
]. The absence of radiation related pulmonary toxicity in our series, may also be attributed to the use of 3-D radiation therapy planning for our patients.